title: Lipid-mediator synthesis in peritoneal macrophages from mice injected with immunostimulants.
abstract: The metabolism of bioreactive lipid mediators was studied in two types of activated macrophages (M phi). We compared the capacity of resident and activated M phi to release, upon a zymosan challenge, cyclooxygenase and lipoxygenase products as well as PAF-acether (platelet-activating factor) and its 2-lyso precursor. Activated M phi were obtained from mice injected intraperitoneally either with nonviable C74 streptococci (St-M phi) or with trehalose dimycolate, a defined immunostimulant isolated from Mycobacterium tuberculosis (TDM-M phi). Both activated populations exhibited common features: conversion of endogenous [14C]arachidonic acid into prostaglandin E2 and thromboxane A2 rather than into prostaglandin I2 and low biosynthesis of PAF-acether, probably due to an impairment of the acetylation step. However, contrary to St-M phi, TDM-M phi did not display a marked overall reduction of arachidonate metabolism. In addition, as compared to resident M phi, TDM-M phi presented a ratio of thromboxane B2/6-ketoprostaglandin F1 alpha 30-fold higher, a better conversion of leukotriene C to leukotriene D and a higher capacity to release the PAF-acether they synthesize. These macrophages thus seem to be valuable tools for studying the formation of mediators and for determining specific markers of an activated state.
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D012898:Autacoids / Q000302:isolation & purification; D005260:Female; D066298:In Vitro Techniques; D008055:Lipids / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000096:biosynthesis; D011453:Prostaglandins / Q000302:isolation & purification; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D012898:Autacoids; D008055:Lipids; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D011453:Prostaglandins; D015054:Zymosan