Showing papers in "Immunopharmacology and Immunotoxicology in 1988"
TL;DR: The purpose of this paper is to review what has been previously published in the field of neuropeptides and to scan the well established modulation of phagocyte functions by opioids.
Abstract: In the past few years it has become evident that neuropeptides may be direct mediators in the modulation of the immune response and the unspecific defense by the brain Lymphocytes have been thought to have opioid receptors and to respond to opioids with an increase in blastogenesis, cytotoxicity and factor release Lymphocytes are said to release various neuropeptides Furthermore, there are some unexplained effects of morphine on the immune system and of the immune system on morphine withdrawal The purpose of this paper is to review what has been previously published in this field The well established modulation of phagocyte functions by opioids will only be scanned
72 citations
TL;DR: The relationship between modifications of the immune response following ingestion of yogurt with live LAB and increased defense mechanisms was confirmed by the bacterial counts in livers and spleens and by the reduced mortality to S. typhimurium infection.
Abstract: The effect of a diet supplemented with yogurt containing live lactobacilli (LAB) - Lactobacillus bulgaricus and Streptococcus thermophilus - on the response of inbred mice to infection with Salmonella typhimurium was elaborated. The results of our experiments were consistent with the hypothesis that modifications of the microflora influence the adherence of S. typhimurium to intestinal mucosa, the natural antibacterial activity of the Peyer's patches lymphocytes, the accumulation of the macrophages in the liver, the proliferative responses of the splenocytes. The relationship between modifications of the immune response following ingestion of yogurt with live LAB and increased defense mechanisms was confirmed by the bacterial counts in livers and spleens and by the reduced mortality to S. typhimurium infection.
41 citations
TL;DR: The results indicate the variable effects a cytotoxic agent can have on lymphoid cells and that dosage is an important parameter for these effects.
Abstract: T-2 toxin, a fungal metabolite shown previously to exert potent immunosuppressive effects, was examined for its effects on activation and interleukin 2 (IL 2) production by murine and rat splenocytes. Splenocytes (1 × 106 cells/well) were incubated with 1 μg Concanavalin A (Con A) for 48h at which time cellular protein and DNA synthesis by these cells were ascertained using radiolabeled precursors. IL 2 synthesis was determined from the cell supernatant using the IL 2-requiring cell line CTLL. Spleen cells from mice treated for 4 consecutive days with 2 mg/kg toxin exhibited a 50% reduction in in vitro Con A activation but the supernatant IL 2 levels from these cells was 4-fold higher than cells from control mice. In vitro exposure of Con A-activated normal spleen cells to various toxin doses for 48h resulted in diminished protein and DNA synthesis at 0.4 ng toxin with maximum inhibition at 1 ng (50% inhibition (TC1D50) - 0.5 ng). Enhanced synthesis of both products was observed at lower toxin con...
40 citations
TL;DR: The results indicate that dopaminergic antagonists may differentially affect lymphocyte proliferative responses to T or B cell mitogens or alloantigens, as well as in terms of receptor specific or non specific phenomenons.
Abstract: The effects of some dopaminergic antagonists were investigated on mouse lymphocyte proliferative responses in vitro. The mixed D1/D2 dopaminergic antagonists chlorpromazine, haloperidol and fIupentixol inhibited 3H-Thymidine incorporation into adult BALB/c mouse spleen cells stimulated by concanavalin A, lipopolysaccharide from Escherichia coli, and allogenic cells in a mixed lymphocyte reaction. The inhibition was achieved at concentrations greater than 10−6M. It was not accounted for by decreased cell viability and it was no longer demonstrable when the compound was added 24h or 48h after the mitogenic stimulus. Conversely selective D2 dopaminergic antagonists sulpiride, metoclopramide and domperidone had no inhibitory effect at concentrations ranging from 10−9 to 10−5 or 10−4M. The three mixed Dl/D2 antagonists inhibited the mitogenic effect of interleukin-1 on concanavalin A-stimulated thymocytes, but not the activity of interleukin-2 on the proliferaiton of the CTLL-2 cell line. The mixed Dl/...
38 citations
TL;DR: The oral treatment with the immunomodulator induced a significant level of protection in CY-immunosuppressed mice to the intranasal infection with P. aeruginosa, when mice were kept at low environmental temperature right after the bacterial challenge.
Abstract: We investigated the effects of an Escherichia coli-derived product (OM-89) in mice. The oral administration of OM-89 led to a significant (p < 0.05. Student's t test) increase in the levels of IgA in intestinal secretions, which was at maximum 25 days after the end of the treatment, when a two-fold increase in IgA levels was observed. The i.p. inoculation of OM-89 induced the stimulation of anti-SRBC plaque-forming cells (PFC) in the spleen. The effect of OM-89 was dose-dependent and produced up to a 9-fold increase in PFC in the treated mice when compared to untreated controls. The oral administration of OM-89 proved to be effective in the enhancement of resistance to challenge i.p. inoculation with E. coli. 32% of OM-89-treated mice showed resistance to this experimental infection at minimal LD100. The combined effects of low environmental temperature and cyclophosphamide (CY) immunosuppression enabled us to enhance differences in survival rates in experiments on the modulation of resistance tow...
36 citations
TL;DR: The most prominent enhancement of NK and ADCC activity was seen in CLL patients, where a dose-related increase was seen (from 0.01 to 1 μg/ml) and lentinan increased NCMC of tumor-bearing subjects.
Abstract: The in vitro effects of lentinan on natural killer (NK), antibody-dependent cell-mediated cytotoxicity (ADCC), lectin-dependent cell-mediated cytotoxicity (LDCC) and mitogen-induced blast transformation were studied in patients with solid tumors and chroyic lymphocytic leukemia (CLL). NK activity was measured against Cr-labelled K-562 targets, ADCC against antibody-coated chicken red cells. LDCC and natural cell-mediated cytotoxicity (NCMC) was assessed using 3H-thymidine prelabelled HEp-2 targets. Mitogen (PHA-and Con A-) induced blast transformation was measured by thymidine incorporation.Blastogenesis and LDCC was not influenced by lentinan. 1 μg/ml lentinan increased NCMC of tumor-bearing subjects. The most prominent enhancement of NK and ADCC activity was seen in CLL patients, where a dose-related increase was seen (from 0.01 to 1 μg/ml).
31 citations
TL;DR: The results suggest that combination therapy including rH-TNF and anti-cancer drugs may be of value in the treatment of malignancy in human patients.
Abstract: A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (rH-TNF) and anti-cancer drugs was demonstrated in vitro. The cytotoxicity of rH-TNF against L-M cells in combination with Mitomycin C (MMC), Adriamycin (ADM), Cytosine arabinoside (Ara-C), Actinomycin D (ACD), Daunomycin (DM), Cisplatin (CDDP), Vincristin (VCR), and 5-Fluorouracil (5FU), based on the concentration necessary for 50% inhibition of cell growth (IC50), was 4 to 347 times as high as that of rH-TNF alone. The results suggest that combination therapy including rH-TNF and anti-cancer drugs may be of value in the treatment of malignancy in human patients.
28 citations
TL;DR: The results suggest that lysosomal enzyme and hydroxyl radicals play an important triggering role in the destruction of tumor cells by TNF, and that the process of destruction might require ATP.
Abstract: The participation of lysosomal enzymes, hydroxyl radicals, and mitochondrial respiration in the cytocidal effect of TNF on tumor cells was investigated. The cytotoxicity of TNF on L-M cells was clearly reduced by lysosomotropic agents, DMSO (hydroxyl radical scavenger), NDGA (lipoxygenase inhibitor), and sodium azide (mitochondrial respiration inhibitor). The results suggest that lysosomal enzyme and hydroxyl radicals play an important triggering role in the destruction of tumor cells by TNF, and that the process of destruction might require ATP.
28 citations
TL;DR: Horeover, supernatants from cultures of monocytes incubated with ProTa(ProTa-sup) were shown to enhance the human auto-NLR either after addition in cultures or after preincubation with responder T lymphocytes.
Abstract: Prothymosin alpha(Prot alpha), an immunologically active polypeptide derived initially from rat thymus, and now pig thymus, was tested for its effect on autoantigen-induced human T cell proliferation in vitro. Pig ProT alpha was found to enhance the autologous mixed lymphocyte response (auto-MLR). Optimum enhancement was achieved at doses which varied among different donors. Treatment of the stimulatory monocytes with ProT alpha resulted in considerably higher auto-MLR responses as compared to those with non treated monocytes. ProT alpha was without effect on T lymphocytes. In contrast, T lymphocytes exhibited enhanced proliferative activity when treated with ProT alpha in the environment of autologous monocytes. Moreover, supernatants from cultures of monocytes incubated with ProT alpha (ProT alpha-sup) were also shown to enhance the human auto-MLR either after addition in cultures or after preincubation with responder T lymphocytes. In addition, ProT alpha-sup did not demonstrate any detectable interleukin 1 (IL 1) or interleukin 2 (IL 2) - like activity. Furthermore, ProT alpha-sup induced an increase in IL 2 production in auto-MLR cultures. The enhancement of T-cell proliferation and IL 2 production by ProT alpha-sup was maximal when this material was added at the beginning of the auto-MLR, and no effect of ProT alpha-sup was seen if the latter was added 3 days after initiation of the culture. Finally, Prot alpha-sup was also shown to increase the expression of IL 2 receptors on T lymphocytes activated in the auto-MLR. These studies suggest that ProT alpha enhances the human auto-MLR through ProT alpha-sup which is released after interaction of monocytes with ProT alpha ProT alpha-sup then increases directly T lymphocyte proliferation by elevating IL 2 production and expression of IL 2 specific receptors on autoactivated T lymphocytes.
19 citations
TL;DR: The complete details of the chemical composition and active components of the ISC should prove useful for biological-response-modification studies and may be under genetic control.
Abstract: Coxiella burnetii, the etiological agent of Q fever, possesses immunomodulatory activity which positively and negatively regulates host immune responses. We wish to determine the Coxiella strain differences and the chemical nature of cellular components suppressing lymphocyte responsiveness. The bacterial components responsible for the immunomodulatory activity are associated with phase I cells. In its natural state, the phase I cell-associated, immunosuppressive complex (ISC) was resistant to chemical and enzymatic treatment. The TSC was inactivated and rendered accessible by chloroform-methanol (CM) (4:1) extraction of phase I cells which produced a CM residue (CMRI) and CM extract (CME). The suppressive components in either CMRI or CME did not induce TSC activity in the host when injected separately. Reconstitution of the CMRI with CME prior to injection produced the same pathological reactions characteristic of phase I cells. The CMRI suppressive component was sensitive to alkali, acid, period...
19 citations
TL;DR: Results indicate that despite low levels of NK activity in pre-weanling mice, MnCl2 is capable of enhancing this activity by 8-9 fold and appears to be mediated by the production of interferon alpha, beta.
Abstract: The effect that MnCl2 has on murine splenic natural killer (NK) cell activity was investigated in infant (10 days old), pre-weanling (18 days old) and weanling (24 days old) C57BL/6J mice. A single intraperitoneal injection of 10, 20 or 40 micrograms MnCl2/g body weight caused a significant enhancement in NK activity, as determined by the in vitro 51Cr release assay. Comparable enhancement of NK activity was observed for age-matched mice injected intraperitoneally with polyinosinic polycytidylic acid (Poly I:C). Both MnCl2 and Poly I:C caused elevations in serum interferon levels. Time-course studies revealed that interferon levels returned to normal within 48 hours following injection with either MnCl2 or Poly I:C; however enhanced NK activity persisted for up to 48 hours in Poly I:C-injected mice and 72 hours in MnCl2-injected mice. The administration of rabbit anti-asialo GMl to MnCl2-injected mice completely abrogated the enhanced NK activity. In addition, the injection of rabbit anti-mouse interferon alpha, beta but not gamma completely abrogated the enhanced NK activity. In addition, the injection of rabbit anti-mouse interferon alpha, beta but not gamma completely abrogated the enhancement of NK activity by MnCl2 and to a lesser extent the enhancement of NK activity by Poly I:C. These results indicate that despite low levels of NK activity in pre-weanling mice, MnCl2 is capable of enhancing this activity by 8-9 fold. Furthermore, Mn-enhanced NK activity in these young mice appears to be mediated by the production of interferon alpha, beta.
TL;DR: Results indicate that, in addition to its previously described inhibitory role in suppressor cell induction, cimetidine is also capable of inhibiting suppressionor cell effector function.
Abstract: The effects of cimetidine upon suppressor cell effector function in a well-studied murine model of contact hypersensitivity were examined Intravenous inoculation of BALB/c mice with DNP-coupled syngeneic spleen cells induced the production of DNP-specific suppressor cells which was demonstrated by a reduction in ear swelling after contact sensitization with l-fluoro-2, 4-dinitrobenzene (DNFB) following transfer of spleen and lymph node cells to naive syngeneic recipients Cimetidine treatment of mice who had also received suppressor cells eliminated the manifestation of suppressor cell activity as measured by the development of normal immunologic response following contact sensitization with DNFB While all the groups receiving cimetidine showed restoration of delayed hypersensitivity, the maximum effect was seen when 50 mg/kg of cimetidine was administered on Day 5 (day of challenge) These results indicate that, in addition to its previously described inhibitory role in suppressor cell inductio
TL;DR: The suppression of the phosphatidylinositol pathway may be involved in the inhibition by CP of lymphocyte blastogenesis induced by concanavalin A (Con A)-stimulation.
Abstract: We have previously demonstrated that the chlorphentermine (CP)1-induced impairment in lymphocyte blastogenesis involves drug-induced inhibition of an event which occurs very early during lymphocyte activation. An early event, which is associated with mitogen-induced lymphocyte activation, involves the hydrolysis of phosphatidylinositol by phospholipase C to yield inositol phosphates and diacylglycerol as products. Inositol phosphates and diacylglycerol then function as mediators of a trans-membrane signal for the continuation of the cellular response. It was the purpose of the present study to determine the effects of CP on this phosphatidylinositol pathway. We demonstrated that formation of inositol phosphates in lymphocytes increases progressively above control over a 2 hour period following concanavalin A (Con A)-stimulation. In contrast, lymphocytes pre-incubated with 10−5M CP for 60 min, then stimulated with Con A for 2 hours in the presence of 10−5M CP, exhibit a significantly depressed inos...
TL;DR: The effect of shosaiko-to observed at an early stage of infection may be T cell-independent, since such an effect was observed in athymic nude mice and delayed footpad reaction could not be detected at such a timing in euthymic normal mice.
Abstract: Lethal effect of Listeria monocytogenes (L monocytogenes) in mice was prevented by an intraperitoneal (ip) injection of a traditional Chinese herbal medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to), 4 days before ip bacterial infection The numbers of bacteria in the peritoneal cavity and liver were smaller in shosaiko-to-treated mice from one day after the infection Macrophage accumulation in the peritoneal cavity after ip inoculation of L monocytogenes was observed in both untreated and shosaiko-to-treated mice Although rates of such increases were almost the same between both groups, the absolute number of macrophages was larger in shosaiko-to-treated than in untreated mice because of a higher level of the macrophage number at 4 days after ip injection of shosaiko-to In untreated mice, bactericidal activity of peritoneal macrophages decreased from one day to 3 days after ip injection of killed L monocytogenes Such an activity was maintained at the same level from 1 to 3 days in shosaiko-to-treated mice Augmented accumulation of macrophages and maintenance of their bactericidal activity may be main mechanisms of the augmented resistance in shosaiko-to-treated mice Augmented resistance against bacterial growth in the thigh muscle in ip shosaiko-to-treated mice may be caused by such mechanisms The effect of shosaiko-to observed at an early stage of infection may be T cell-independent, since such an effect was observed in athymic nude mice and delayed footpad reaction could not be detected at such a timing in euthymic normal mice
TL;DR: Results indicate that Quadrol promotes in vivo collagen synthesis and that Quadrology may be effective as a stimulator of wound healing in diabetic and non-diabetic animals.
Abstract: The rate of collagen deposition in implanted polytetrafluoroethylene (PTFE) tubing in non-diabetic and streptozotocin-induced (STZ) diabetic mice was measured during 14 days post-wounding. At the time of implantation, test groups received injections of either Quadrol [N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine], glucan, or buffer in an area adjacent to the wound site. The accumulation of collagen in the implants of Quadrol-treated non-diabetic animals was more than 200% above control on days 8 to 11 and was 50% above control on day 14. In Quadrol-treated STZ-diabetic mice, the collagen accumulation gradually increased from 50% above control on day 8 to 200% above control on day 14. Treatment with glucan increased the collagen accumulation in normal mice 200 to 300% above control from days 8 to 11 respectively and then 30% above control on day 14. Collagen accumulation in the implants of the glucan-treated STZ-diabetic mice was similar to the control group. These results indicate that Quadrol promotes in vivo collagen synthesis and that Quadrol may be effective as a stimulator of wound healing in diabetic and non-diabetic animals.
TL;DR: The data suggest that lithium salts produce a modulation of natural killer activity of mouse spleen cells, probably through a mechanism involving the increase of the number of NK-precursors in hosts not subjected to cytotoxic chemotherapy.
Abstract: The in vivo and in vitro influence of lithium lactate on mouse natural killer activity was investigated In vitro exposure of effector-target mixture to graded concentrations of lithium did not substantially modify the natural killer activity of mouse splenocytes, untreated or pretreated with cyclophosphamide However in vitro treatment of effector splenocytes increased the frequency of NK-percursor cellsThe in vivo treatment with lithium lactate greatly increased the natural killer activity in intact mice, whereas it did not improve this cytotoxic function in host immunodepressed by cyclophosphamideThese data suggest that lithium salts produce a modulation of natural killer activity of mouse spleen cells, probably through a mechanism involving the increase of the number of NK-precursors in hosts not subjected to cytotoxic chemotherapy
TL;DR: The data show that BP disrupts the maternal T cell repertoire, leading to an accumulation of Lyt 1-2+ cells, and suggest that splenic disruption may be due to changes in the differentiation potential of T precursor cells.
Abstract: Progeny from benzo(a)pyrene (BP) mposed (150 ug/g body weight) primiparous mothers, injected during the second trimester of pregnancy, are severely compromised immunologically. In view of maternal-fetal associations, we studied, during pregnancy and postpartum, the quantitative and functional status of the maternal T cell population in the thymus and/or spleen. In the thymus, there is an exacerbated depression in the amounts of thymocytes, (tH+, Lyt 1+, Lyt 2+ cells) during pregnancy relative to the corn oil-injected controls, which is sustained postpartum. In the spleen, while there are inconsistencies in the level of θ+ cells, The Lyt 1+ are depressed postpartum relative to virgins, but the Lyt 2+ are enhanced during pregnancy and postpartum, reaching levels <700-fold of controls. In controls, while the number of Lyt 1+ cells was higher than BP-exposed mice or virgins during pregnancy, they virtually disappeared postpartum. A similar but reversed image is mirrored by the Lyt 2+ cells, i.e., they...
TL;DR: AZT Levels on day 14 were significantly higher than the corresponding levels on day 7, resulting in a 2-fold increase of the area under the serum concentration-time curve (AUC) and a prolongation of the mean half-life of AZT (44 to 70 min) during the INPX treatment.
Abstract: 3'-azido-3'-deoxythymidine (AZT) was administered orally to 8 AIDS patients at a dose of 100 mg every 6 hours for 14 days. On days 8–14 the patients were also given lginosine-pranobex (INPX) every 6 hours. On day 7, while the subjects were taking AZT alone and on day 14 while they were receiving AZT + INPX, blood samples were obtained over a 6-hour dosing interval for measurement of AZT by a specific AZT radioimmunoassay. AZT levels on day 14 were significantly higher than the corresponding levels on day 7, resulting in a 2-fold increase of the area under the serum concentration-time curve (AUC) and a prolongation of the mean half-life of AZT (44 to 70 min) during the INPX treatment. INPX is an immunomodulatory drug with an inhibitory effect on HIV. The potential advantages of a combined treatment AZT+INPX are: 1) need for lower dose of AZT for maintaining a therapeutic anti-retroviral level; 2) a longer interval period between AZT treatments; 3) a potential to enhance immunological response resul...
TL;DR: It is suggested that SATM inhibits the stimulatory effects of IL-2 on T cells partly by interfering withIL-2 receptor expression, and partly by other mechanisms of action.
Abstract: We studied the effects of the gold compound sodium aurothionalate (SATM) on the responses of murine CTLL2 cells, and human T cells to Interleukin-2 (IL-2). SATM inhibited tritiated thymidine (3HTdR) incorporation by CTLL2 cells stimulated with human recombinant IL-2. Human T cells were cultured with phytohemagglutinin (PHA) in separate experiments and IL-2 receptor expression measured by using immunofluorescent anti-Tac serum; SATM inhibited IL-2 receptor expression. Furthermore, SATM when added concurrently with PHA, and IL-2 inhibited 3HTdR incorporation by human T cells in 5 day cultures. The kinetics of inhibition were further studied by adding PHA to T cells for 48 hours fllowed by the addition of SATM and IL-2; SATM inhibited 3HTdR incorporation even though receptor expression had occurred. These results suggest that SATM inhibits the stimulatory effects of IL-2 on T cells partly by interfering with IL-2 receptor expression, and partly by other mechanisms of action. These effects of SATM may...
TL;DR: Investigation on the effect of TNF on RNA and protein synthesis by tumorigenic and normal cell lines showed their synthesis in tumor cells to be increased at 12 h and to peak at 24 h of incubation with TNF, thus suggesting the existence of a defense mechanism in normal, TNF-resistant cells which is absent or greatly weakened in tumor Cells.
Abstract: Investigation on the effect of TNF on RNA and protein synthesis by tumorigenic and normal cell lines showed their synthesis in tumor cells to be increased at 12 h and to peak at 24 h of incubation with TNF, while that in normal diploid fibroblast (HEL) cells was apparently unaffected by the presence of TNF. The increase correlated with cell susceptibility to cytotoxic effect by TNF. Artificial inhibition of either RNA or protein synthesis by L-M cells. by addition of artinomycin D or cycloheximide, increased the cytotoxic effect of TNF and thus suggested that the elevated RNA and protrin synthesis is related not, to the cytotoxic reaction itself but rather to a defense mechanism. Similar incubaticin of HEL cells with TVF in the presence of either inhibtor resulted in the occurrence of cytotoxicity not observed with TNF alone, thus suggesting the existence of a defense mechanism in normal, TNF-resistant rolls which is absent, or greatly wealtend in tumor cells.
TL;DR: It is concluded that prostaglandin E1, Misoprostol, and 16,16-dimethyl PGE2 can function as immunosuppressive reagents both in vitro and in vivo and in the future they may serve to augment existing forms of immunOSuppressive therapy.
Abstract: In this study the ability of prostaglandin E1 (PGE1), Misoprostol (a stable analog of PGE1), and 16,16-dimethyl PGE2 (a stable analog of PGE2) to suppress immune responses in vitro and in vivo was determined. All of the compounds caused a titratable (10(-6) to 10(-9) M) suppression of Con A blastogenesis and the mixed lymphocyte response whereas there was only slight inhibition of the LPS response. When either 16,16-dimethyl PGE2 (30 ug/mouse) or Misoprostol (60 ug/mouse) was administered daily in vivo, there was a significant suppression of splenomegaly in F1 mice (C57Bl/6 x CBA) which had been injected with parental (C57Bl/6) spleen cells. We conclude that prostaglandins of the E series can function as immunosuppressive reagents both in vitro and in vivo. In the future they may serve to augment existing forms of immunosuppressive therapy.
TL;DR: It is concluded that the therapeutic effect of OK-432 induced endogenous TNF on tumor bearing mice and cancer patients was investigated and may well be taken into account in treatment of cancer.
Abstract: The therapeutic effect of OK-432 induced endogenous TNF on tumor bearing mice and cancer patients was investigated.OK-432 (10 KE/mouse) was administered intraperitoneally to Balb/c mice 7 days prior to the transplantation of Meth A cells (1×106/mouse) into the abdominal cavity. And at day 1 of tumor inoculation, 1 KE/mouse of OK-432 was administered intraperitoneally.The significant prolongation of life span was observed in these mice.On the basis of these observation, therapeutic effect of endogenous TNF on cancer patients was clinically evaluated. OK-432 was administered intraperitoneally or intrapleurally to cancer patients with peritonitis carcinomatosa or pleuritis carcinomatosa 4 times (10KE each) every other day and 50KE of OK-432 was readministered with the interval of 7 days.An appreciable activity of TNF was detected in peritoneal fluids or pleural effusion, and the significant decreasing of these fluids was observed. It is therefore concluded that these therapeutic approach may well be ...
TL;DR: Two large fragments, I and II, have been isolated and identified as C-terminal peptides located at sequence positions between 79–234 and 107–234, their molecular weights determined by electro-phoretic mobility on SDS gel were 16,000 and 14,000 daltons.
Abstract: Purified plant protein, Trichosanthin (TCS), was partially digested with chymotrypsin to produce peptide fragments. Two large fragments, I and II, have been isolated and identified as C-terminal peptides located at sequence positions between 79–234 and 107–234, Their molecular weights determined by electro-phoretic mobility on SDS gel were 16,000 and 14,000 daltons. Studies using fluorescence quenching measurements by titrating anti-TCS Fab with TCS and fragment I and II showed that four epitopes were present in intact TCS and one each epitope in fragment I and II. One of the epitopes is therefore located between sequence positions 107 and 234.
TL;DR: 5-LPO inhibitors, but not selective FCO inhibitors (ibuprofen and indomethacin), suppressed lymphoproliferation at nontoxic concentrations, suggesting that products of the 5-L PO pathway may mediate the thymocyte proliferative response induced by IL-1/PHA.
Abstract: A variety of cyclooxygenase (FCO) and 5-lipoxygenase (5-LPO) inhibitors were tested for their ability to modulate murine thymocyte proliferation induced by IL-1 and suboptimal levels of the mitogen phytohemagglutinin (PHA) The contribution of drug toxicity to inhibition of 3H-thymidine incorporation was estimated by measuring MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) formazan production in the thymocyte cultures at the end of the assay Cyclosporin A and dexamethasone, two positive control compounds, potently inhibited thymocyte proliferation at extremely low concentrations (001 and 0001 μg/ml respectively), although activity roughly paralleled toxicity In contrast, 5-LPO inhibitors (AA-861, BW-755c, and ETYA), but not selective FCO inhibitors (ibuprofen and indomethacin), suppressed lymphoproliferation at nontoxic concentrations, suggesting that products of the 5-LPO pathway may mediate the thymocyte proliferative response induced by IL-l/PHA Attempts to counteract
TL;DR: Analysis of cellular effector function(s) often requires their isolation from other cellular types, and cell separatory techniques could mask, or select out, clinically important functional lesions.
Abstract: Analysis of cellular effector function(s) often requires their isolation from other cellular types. Cell separatory techniques could mask, or select out, clinically important functional lesions. We examined differences in canine peripheral blood neutrophil functions, i.e. migration and H202 production, following two commonly used cell separation techniques: isotonic lysis or density gradient (Percoll) centrifugation. Separation methodology was observed to have a significant impact on both metabolic and mobility functions. In comparison to isotonic lysis, Percoll separation caused near 100% increases in random migration, near 40% decreases in chemotaxis and 70% increases in H202 production.
TL;DR: Depression in white blood cells is attributed to lymphocyte depletion since the granulocytes were virtually unchanged and the lymphocyte to granulocyte ratio, ordinarily >2 was 1 or < one.
Abstract: Pregnant C3H/Anfcum mice were injected ip with 150 ug benzo-(a)pyrene (BP)/g body weight at the second trimester (12 days). Quantitative and differential changes were assayed in the peripheral blood leukocytes and erythrocytes at various times before and after mating and treatment. Within 5 days after injection, a 2- to 4-fold reduction in leukocytes was observed when compared to controls [corn oil (vehicle for BP)-injected pregnant females] which persisted into the 10th postpartum day. The erythrocytes were also significantly reduced but not to the same degree (1.2- to 1.5-fold). Depression in white blood cells is attributed to lymphocyte depletion since the granulocytes were virtually unchanged and the lymphocyte to granulocyte ratio, ordinarily >2 was 1 or < one. No change in monocytes was observed and none of the cell populations, including the erythrocytes, appeared to be abnormal (e.g., no increase in reticulocytes). A moderate reduction (1.5-fold) in erythrocytes and leukocytes also occurre...
TL;DR: The results suggest that in this GVH model the development of an immunodeficient state is directly related to the induction of an active T suppressor cell population and that such cells are effectively eliminated from the splenocyte population following treatment with some immunosuppressive drugs.
Abstract: The pathologic features of the acute graft-vs-host disease occurring in unirradiated (C57B1/6 X A/J)F1 mice injected intravenously with lymphocytes from the C57B1/6 parent are similar to those reported for other parental → F1 hybrid combinations.When stimulated in culture with concanavalin A, lipopolysaccharide or alloantigen, spleen cells from B6AF1 mice that had been injected 11 days previously with B6 lymphocytes exhibited proliferative responses that were drastically reduced in comparison to the responses of spleen cells from F1 hosts injected with syngeneic lymphocytes. IL2 production in h7H spleen cell cultures was also diminished. Proliferative responses and IL2 production were partially restored in mice given immunosuppressive therapy with azathioprine, cyclosporin A or Sch 24937 a drug whose inhibitory effects on cellular and humoral immune responses in mice have recently been described.Phenotypic analyses by flow cytometry of the GVH splenocyte population indicated that the most consiste...
TL;DR: Results indicate that, at appropriate concentrations, mafosfamide can effect the elimination of GvHD-causing T lymphocytes from donor bone marrow inocula without compromising its engraftment potential.
Abstract: Murine splenocyte-supplemented bone marrow cell suspensions were incubated with mafosfamide, an analog of “activated” cyclophosphamide, prior to transplantation across major histocompatibility barriers into lethally-irradiated recipient mice in an attempt to reduce the incidence of graft-versus-host disease (GvHD)-related mortality without compromising engraftment. Irradiated mice that received vehicle-treated splenocyte-supplemented bone marrow inocula developed symptoms of severe GvHD; the majority of such animals did not survive. Treatment of donor cells with 160 μM mafosfamide for 30 min resulted in a marked increase in animal survival without evidence of GvHD. Survival of bone marrow allografts was demonstrated by the persistence of donor-type mononuclear cells in the peripheral blood of surviving animals. Treatment of donor cells with a four-fold higher concentration of mafosfamide also resulted in a significant increase in survival without evidence of GvHD; however, host resistance to engra...
TL;DR: A pattern of responses implicates Aroclor 1254 in the activation of eicosanoid metabolism as it matches the differential responses reported for arachidonic acid.
Abstract: A human whole blood chemiluminescence (CL) assay was established using zymosan as cell activator. Aroclor 1254 was found to inhibit this CL response in a direct linear relation to its concentration, (50% inhibitory dose, (ID50) equal to 5 × 10−4 M) in diluted blood samples of 10 normal human subjects. In comparison the ID50 of other inhibitors was 1.3 × 10−3 M for ethylenediamine tetraacetic acid, 3.3 × 10−3 M for ascorbic acid, 4 × 10−3 M for reduced glutathione, 1.2 × 10−3M for ethanol, 2.5 × 10−1 for methanol and 3.7 × 10−1 M for dimethyl sulfoxide. Using 12-o-tetradecanoyl-phorbol-13-acetate (TPA) as cell activator the CL response was likewise inhibited by Aroclor 1254 with an ID50 of 4.5 × 10−4 M. However, it was found that Aroclor 1254 alone has a stimulatory CL effect on otherwise unactivated cells. To compare the mechanisms involved in the CL elicited by the three stimulants zymosan, TPA and Aroclor 1254, the CL signal was measured in the presence of cytochalasin B. Cytochalasin B inhibite...
TL;DR: It is shown that the neocortex influences the changes induced by an immunopotentiator, sodium diethyldithiocarbamate Cirnuthiol), on the MHC antigen content on mouse T cell- surface.
Abstract: The induction of T-cell responses involves the recognition of extrinsic antigens in association with antigens of the major histocompatibility complex (MHC) The present results demonstrate that the lateralized control exerted by the brain neocortex on T-cell activities extends to the expression of MHC antigens, yet differently on spleen or lymph node T cells This study also shows that the neocortex influences the changes induced by an immunopotentiator, sodium diethyldithiocarbamate Cirnuthiol), on the MHC antigen content on mouse T cell- surface