/pdf/secretory-products-of-macrophages-5cf7rlxshh.pdf

Secretory products of macrophages.

(First of Two Parts) THE part played by phagocytes in defense against invading pathogens has been recognized since 1883. In that year, Metschnikoff, a Russian zoologist, reported that foreign particles injected into metazoans (in Metschnikoff's experiments, starfish larvae) were taken up by a population of "wandering mesodermal cells" that resided in interstitial tissues.1 He postulated a crucial role in host defense for these wandering cells, which he named "phagocytes." Since Metschnikoff's discovery, hundreds of scientists studying dozens of species have reported thousands of studies on these cells, perhaps the most widely recognized of which are those of the eminent English . . .

Oxygen-dependent microbial killing by phagocytes (second of two parts).

Few nonphagocytic cells are known to generate reactive oxygen intermediates. Based on horseradish peroxidase-dependent, catalase-inhibitable oxidation of fluorescent scopoletin, seven human tumor cell lines constitutively elaborated H2O2 at rates (up to 0.5 nmol/10(4) cells/h) large enough that cumulative amounts at 4 h were comparable to the amount of H2O2 produced by phorbol ester-triggered neutrophils. Superoxide dismutase-inhibitable ferricytochrome c reduction was detectable at much lower rates. H2O2 production was inhibited by diphenyleneiodonium, a flavoprotein binder (concentration producing 50% inhibition, 0.3 microM), and diethyldithiocarbamate, a divalent cation chelator (concentration producing 50% inhibition, 3 microM), but not by cyanide or azide, inhibitors of electron transport, or by agents that inhibit xanthine oxidase, polyamine oxidase, or cytochrome P450. Cytochrome b559, present in human phagocytes and lymphocytes, was undetectable in these tumor cells by a sensitive spectrophotometric method. Mouse fibroblasts transfected with human tyrosinase complementary DNA made melanin, but not H2O2. Constitutive generation of large amounts of reactive oxygen intermediates, if it occurs in vivo, might contribute to the ability of some tumors to mutate, inhibit antiproteases, injure local tissues, and therefore promote tumor heterogeneity, invasion, and metastasis.

https://cancerres.aacrjournals.org/content/canres/51/3/794.full.pdf

Production of Large Amounts of Hydrogen Peroxide by Human Tumor Cells

Indirect evidence suggests accelerated degradation of endothelium-derived nitric oxide (ENDO) by superoxide anion (O2-) in hypercholesterolemic vessels (HV) To directly measure O2- production by normal vessels (NV) and HV, we used an assay for O2- based on the chemiluminescence (CL) of lucigenin (L) HV (1 mo cholesterol-fed rabbits) produced threefold more O2- than NV (147 +/- 020 nM/mg tissue/min, n = 7 vs 052 +/- 005 nmol/mg tissue/min, n = 8, P < 0001) Endothelial removal increased O2- production in NV (073 +/- 008, n = 6, P < 005), while decreasing it in HV (076 +/- 015, n = 5, P < 005) There was no difference between denuded HV and denuded NV Oxypurinol, a noncompetitive inhibitor of xanthine oxidase, normalized O2- production in HV, but had no effect in NV In separate isometric tension studies treatment with oxypurinol improved acetylcholine induced relaxations in HV, while having no effect on responses in normal vessels Oxypurinol did not alter relaxations to nitroprusside Thus, the endothelium is a source of O2- in hypercholesterolemia probably via xanthine oxidase activation Increased endothelial O2- production in HV may inactivate endothelium-derived nitric oxide and provide a source for other oxygen radicals, contributing to the early atherosclerotic process

/pdf/hypercholesterolemia-increases-endothelial-superoxide-anion-1rnwngjon2.pdf

Hypercholesterolemia increases endothelial superoxide anion production.

Only women with symptoms need to have their breast implants removed, says government

A number of highly reactive oxygen species have been implicated in the oxygen-dependent mechanisms involved in bactericidal activity of phagocytic leukocytes Hydrogen peroxide and superoxide, two agents known to occur during phagocytosis, are thought to interact to generate hydroxyl radical, singlet oxygen, and other potentially reactive molecules Using an assay system of ethylene generation from methional, cell preparations of human monocytes were demonstrated to generate hydroxyl radical or a similar agent during phagocytosis of zymosan particles The generation of ethylene was impaired by agents which reduce superoxide or hydrogen peroxide concentrations as well as by agents reported to be hydroxyl radical scavengers The ethylene generation did not appear to be dependent on myeloperoxidase in that azide enhanced ethylene generation Monocytes from a patient with chronic granulomatous disease failed to generate ethylene during phagocytosis This assay technique may be useful in exploring the metabolic events integral to the bactericidal and inflammatory activity of phagocytic leukocytes

/pdf/evidence-for-hydroxyl-radical-generation-by-human-monocytes-5a2p10jizb.pdf

Evidence for hydroxyl radical generation by human Monocytes.

Recent studies indicate that oxygen radicals such as superoxide or singlet oxygen may be important in the functional activity of human granulocytes. We have examined the possible importance of these radicals in the functional capacity of human blood monocytes. Monocytes, like granulocytes, generate chemiluminescence during phagocytosis. Chemiluminescence is impaired 50-90% by superoxide dismutase, an enzyme which enhances the dismutation of superoxide to hydrogen peroxide. These results indicate that superoxide is related to the chemiluminescence generated by monocytes. Superoxide dismutase in a concentration which impaired chemiluminescence also impaired the staphylococcal killing by monocytes. Hexose monophosphate shunt activity and hydrogen peroxide production by granulocytes and monocytes were also evaluated. The oxidation of [1-14C]glucose was used as a measure of hexose monophosphate shunt activity and the oxidation of [14C]formate as an estimation of hydrogen peroxide production. The oxidation of both substrates by monocytes was increased during phagocytosis but, in contrast to results in granulocytes, was not further increased by the addition of superoxide dismutase. These data indicate that superoxide may be important in bactericidal activity of human monocytes. Our results also suggest that the metabolism of oxygen radicals in monocytes and granulocytes may be different.

/pdf/a-comparison-of-the-metabolic-response-to-phagocytosis-in-1t49pv7pp8.pdf

A comparison of the metabolic response to phagocytosis in human granulocytes and monocytes.

Leukemic reticuloendotheliosis: A study of the origin of the malignant cell

Although adherence to glass is commonly used to prepare monocyte monolayers from blood mononuclear cell suspensions (1–3), several recent reports suggest that lymphocytes are also able to adhere to either glass or glass substitutes like nylon or tissue culture dishes (4, 5). Using morphologic criteria, Levis (4) reported considerable lymphocyte binding to glass coverslips placed in mononuclear cell suspensions. Although many of the lymphocytes could be detached by rigorous mechanical washing, this resulted in a loss of monocytes as well. Rosenthal (5) has suggested that adherence to glass can be used to deplete selectively lymphocyte preparations of antibody-forming or “bursal-derived” (B) 2 lymphocytes. Similarly, Boldt (6) has demonstrated that nylon columns can remove from a suspension of blood mononuclear cells a population of lymphocytes which are “highly responsive” to concanavalin A. These observations indicate that monocyte monolayers prepared by adherence of blood mononuclear cells to glass or tissue culture dishes may be contaminated by considerable numbers of lymphocytes.

Characterization of Glass Adherent Human Mononuclear Cells

The results of the present study emphasize the importance of minimizing the time delay between a significant elevation in CEA and a second-look operation. Equally important are the frequency of serial determinations, a thorough understanding of the limitations of the assay, and careful evaluation of the clinical condition of the patient.

Gerald W. King

Papers

Evidence for hydroxyl radical generation by human Monocytes.

A comparison of the metabolic response to phagocytosis in human granulocytes and monocytes.

Leukemic reticuloendotheliosis: A study of the origin of the malignant cell

Characterization of Glass Adherent Human Mononuclear Cells

A retrospective and prospective study of serial CEA determinations in the early detection of recurrent colon cancer