Dynamics of arachidonic acid metabolism in macrophages from delayed-type hypersensitivity (Schistosoma mansoni egg) and foreign-body-type granulomas.
The present study examines the kinetics of arachidonic acid (AA) metabolism by murine macrophages isolated from sites of experimentally induced pulmonary granulomatous inflammation. Macrophages of T-cell-mediated hypersensitivity lesions induced by Schistosoma mansoni eggs (SE-GM) and non-T-cell-mediated foreign-body-type lesions (FB-GM) induced by Sephadex beads were examined. Overall, macrophages from both types of lesions produced mainly lipoxygenase pathway metabolites, leukotrienes, and monohydroxyeicosatetraenoic acids (mono-HETEs). Early after induction (4 days [4D]), SE-GM showed an augmented zymosan-stimulated AA release and metabolism compared to resident peritoneal macrophages. Macrophages from mature lesions (8-32D) showed constitutive synthesis of metabolites and were refractory to zymosan stimulation. Both SE-GM and FB-GM showed augmented AA uptake incorporating a large proportion into neutral lipids. A direct comparison of SE-GM and FB-GM revealed that the T-cell-mediated lesion produced lesser amounts of prostaglandins and leukotrienes and showed reduced incorporation of AA into phosphatidylcholine. These data suggest that AA metabolism by granuloma macrophages is sequentially modified during recruitment and activation at sites of chronic inflammation.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D005260:Female; D005549:Foreign-Body Reaction / Q000378:metabolism / Q000473:pathology; D006099:Granuloma / Q000378:metabolism* / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D010063:Ovum / Q000276:immunology; D010743:Phospholipids / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology
D001095:Arachidonic Acids; D010743:Phospholipids; D016718:Arachidonic Acid; D015054:Zymosan