Showing papers by "Per Venge published in 1986"

Mechanism of membrane damage mediated by human eosinophil cationic protein.

Abstract: Recent evidence suggests a role for eosinophil granule proteins in contact-dependent antibody-mediated cytotoxicity. Cytolysis may involve a secretory phenomenon whereby granule proteins are released at the site of contact between eosinophil and target cells. Several basic proteins have been isolated from eosinophil granules, including the major basic protein, eosinophil cationic protein, eosinophil protein-X and eosinophil peroxidase. One of the major granule proteins of human eosinophils is the eosinophil cationic protein (ECP) which has been shown to damage schistosomula of Schistosoma mansoni at concentrations as low as 10(-7). Here, we describe the formation of functional channels by purified human ECP. The transmembrane pores formed by ECP are relatively voltage-insensitive and non-ion-selective, suggesting a role for channel formation by ECP in target cell damage mediated by eosinophils. Channel formation by granule proteins of immune effector cells may represent a general and effective mechanism of target cell killing.

Chemotactic activity of LTB4 in man.

Abstract: An improved skin window chamber technique has been developed and used for a quantitative study of the chemotactic effect of leukotriene B4 (LTB4). LTB4 (0.5 microM) was exposed to a skin window on the forearm of eight healthy volunteers, while phosphate buffered saline served as control in a skin window on the other forearm. Skin window exudates and samples of blood draining the skin window areas were collected after 1, 2, 4, 8, and 24 h. The samples were quantitated for the different types of leukocytes as well as the intra- and extracellular concentration of the eosinophilic cationic protein and lactoferrin as markers of eosinophil and neutrophil granulocytes. A significantly increased migration of neutrophil granulocytes into the skin window chamber containing LTB4 was found from the 2nd to the 8th hour after the initial LTB4 exposure. The eosinophils reached a significant peak at the 4th hour. The rise in the actual number of eosinophil cells did not reach significance, whereas measurements of the eosinophilic cationic protein in the cellular fraction of the exudate exhibited a significant increase as a reflection of the number of eosinophils. This highlights the potential clinical value of eosinophilic cationic protein measurements to reveal eosinophilia instead of the traditional eosinophil counts. Extracellular eosinophilic cationic protein and lactoferrin did not change significantly in the LTB4-exposed skin window, implying that LTB4 does not activate the eosinophils and neutrophils to exocytosis of their enzymes. The present in vivo results support the concept of LTB4 being a potent chemoattractant to neutrophil and less so to eosinophil granulocytes in humans, a chemoattractant that recruits the leukocytes but does not seem to activate them.

Ankylosing spondylitis: a chronic inflammatory disease with iron overload in granulocytes and platelets.

Abstract: The cellular stores of iron in granulocytes and platelets isolated from 29 patients with ankylosing spondylitis were measured by the nuclear microprobe technique. The mean iron content in polymorphonuclear cells (PMNs) was 32 (SD 3) micrograms/g dry weight and in platelets 11 (2.6) micrograms/g dry weight. Corresponding values for age and sex matched healthy controls were 5.2 (1.9) and 4.6 (0.8) micrograms/g (p less than 0.001). Significant correlations were found in the patient group between (PMN) iron and the circulating levels of transferrin, total iron, and lactoferrin (p less than 0.05). PMN iron was not related to serum ferritin. Platelet iron correlated with transferrin (p less than 0.01) but not with the other iron binding proteins. Significant relationships were also found between the PMN iron stores and the inflammatory activity defined by erythrocyte sedimentation rate (ESR) and the immunoglobulins A and G. These data further illustrate the altered iron kinetics in chronic inflammatory disease and record the fact that the redistribution of iron associated with the inflammatory process also includes granulocytes and platelets.

Myocardial and skeletal muscle function in habitual alcoholics and its relation to serum myoglobin

Abstract: Lower-than-normal serum myoglobin levels are regularly found in habitual alcoholics without recent alcohol intake and were also confirmed in this study. It was hypothesized that these low levels reflect reduction in myocardial and skeletal muscle function. To study this hypothesis, heart and skeletal muscle function was evaluated and related to serum myoglobin levels. Myocardial function evaluated by non-invasive techniques was significantly decreased and heart muscle mass increased (p

An immunofluorescent method for a specific demonstration of granulocytes and some of their proteins (ECP and CCP).

Abstract: Using p-benzoquinone as a fixative the non-specific fluorescence of granulocytes and especially the eosinophils is removed for both FITC and TRITC. In this way we have been able to detect the eosinophil cationic protein (ECP) and the chymotrypsin-like cationic protein (CCP) in human lung tissue and by double immunofluorescent labelling shown that these two proteins very likely are related to eosinophils respectively the neutrophils.

Patient Reactions and Granulocyte Degranulation during Hemodialysis with Cuprophane and Polycarbonate Membranes

Abstract: During dialysis with cuprophane or polycarbonate filters, a fall in neutrophil and eosinophil cell counts is observed. Total complement remains unchanged, but C3a increases indicating complement activation. Release of granular granulocyte proteins is observed indicating granulocyte activation. Patient reactions or biochemical findings indicate no significant difference when polycarbonate or cuprophane membranes are used, except perhaps less complement activation with polycarbonate. The biochemical observations may be due to complement activation or cell contact with the membrane.

The chemokinetic inhibitory factor derived from chronic lymphocytic leukaemia cells : Partial purification and characterization of a new lymphokine

Abstract: We have recently described a heat-labile and cell-directed neutrophil migration inhibitory activity that is present in serum from patients with chronic lymphocytic leukaemia (CLL). The inhibitory activity is produced and secreted by CLL cells in vitro. In the present study the inhibitory activity was partially purified from short-term cultures of monoclonal leukaemic B-CLL cells. On gel filtration the calculated molecular weight was apparently 30,000. By anion exchange chromatography, the inhibitory factor was recovered in the fractions that eluted with 0.3 mol/l NaCl. The active material applied to preparative agarose gel electrophoresis migrated towards the anode. The inhibitory factor was totally destroyed by trypsin. In addition it bound to concanavalin A-Sepharose. These properties indicate that the inhibitory factor is a glycoprotein. Antibodies against the isolated inhibitory factor were raised in rabbits. CLL serum was separated by means of gel filtration and the inhibitory activity was recovered in the pool with a molecular weight of approximately 30,000. The activity was completely neutralized by the antibodies raised against the CLL-cell-derived inhibitor, indicating the similarity between this and the serum-derived inhibitor. We have shown the existence of a new lymphokine, derived from B-CLL cells, in serum from patients with CLL.