Phospholipase A2, an in vivo immunomodulator.
Arachidonic acid (AA) can be released from membrane phospholipids by the action of phospholipase A2 (PLA2). There is evidence that unsaturated fatty acids, particularly AA, released from membrane phospholipids are required to activate the respiratory burst of macrophages. The data reported here indicate that peritoneal macrophages harvested 30 min after i.p. injection of PLA2 can phagocytose Candida albicans more efficiently and emit more chemoluminescence (CL) than normal cells when stimulated by zymosan. PLA2 injection also enhances the CL of peritoneal cells from mice already stimulated by immunomodulators such as trehalose dimycolate (TDM), bestatin, or oncostatic drugs such as aclacinomycin (ACM). CL is not sensitive to potassium cyanide (KCN), but is inhibited by catalase, superoxide dismutase (SOD), nordihydroguaiaretic acid (NDGA) and high doses of indomethacin (10(-3) M). In vivo PLA2 treatment stimulates the synthesis of both cyclooxygenase and lipoxygenase derivatives of AA metabolism (PGE2, 6-keto, PGF1 alpha TXB2 and LTC4). Inhibitors of AA metabolism (NDGA, indomethacin) modulate the production of free oxidizing radicals in this experimental model, partly because of their effect on AA metabolism, as determined by the measuring immunoreactive products. However, this work indicates that the effects of these inhibitors, which have been extensively used in CL studies, should be interpreted with caution, since their specificity for AA metabolism is relative.
Bravo Cuellar
A
A
Institut de Cancérologie et d'Immunogénétique (Univ. Paris-Sud, Ass. Cl. Bernard & ARC), Hôpital Paul-Brousse, Villejuif, France.
Homo-Delarche
F
F
Orbach-Arbouys
S
S
D000276:Adjuvants, Immunologic; D000818:Animals; D002176:Candida albicans / Q000276:immunology; D016861:Cyclooxygenase Inhibitors; D000431:Ethanol / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008163:Luminescent Measurements; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity; D010587:Phagocytosis; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D011190:Potassium Cyanide / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D013482:Superoxide Dismutase / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D000431:Ethanol; D013482:Superoxide Dismutase; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D011190:Potassium Cyanide