Induction of endogenous arachidonic acid metabolism in human neutrophils with snake venom phospholipase A2, immune complexes, and A23187.
The stimuli responsible for eicosanoid secretion of phagocytes in chronic inflammatory disorders like rheumatoid arthritis and chronic inflammatory bowel disease are unknown. Phospholipase A2 (PLA2), found in Russelli vipera snake venom, has been proposed to be more than 100 times more potent on a molar basis than A23187 in releasing leukotriene B4 (LTB4) from porcine neutrophils. Therefore, this enzyme was investigated as a challenger of human neutrophils (PMNs) and compared with immune complexes and A23187. 1-14C-Arachidonic acid (AA) was incorporated into purified human PMNs until steady state conditions were obtained. AA release and metabolism were stimulated with either PLA2 isoenzyme of Russelli vipera, immune complexes, or A23187. The radioactive eicosanoids released were extracted and separated by thin layer chromatography, followed by autoradiography and quantitative laser densitometry. Stimulation with PLA2, immune complexes, or A23187 resulted in LTB4 formation of 0%, 1.8%, and 5.3%, respectively, of total released radioactivity. In conclusion, Russelli vipera PLA2 does not stimulate AA-release and metabolism in human PMNs, and immune complexes are weak as compared to the unphysiologic challenger A23187 in this respect.
Langholz
E
E
Department of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Denmark.
Nielsen
O H
OH
D000936:Antigen-Antibody Complex; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007527:Isoenzymes / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000378:metabolism; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D013745:Tetanus Toxoid / Q000276:immunology; D014757:Viper Venoms / Q000494:pharmacology*
D000936:Antigen-Antibody Complex; D001095:Arachidonic Acids; D007074:Immunoglobulin G; D007527:Isoenzymes; D013745:Tetanus Toxoid; D014757:Viper Venoms; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2