PNEUMOCYSTIS-CARINII INDUCES THE RELEASE OF ARACHIDONIC-ACID AND ITS METABOLITES FROM ALVEOLAR MACROPHAGES

Pneumocystis carinii is an opportunistic organism that causes severe l ung injury in immunocompromised hosts. Macrophage responses to P. cari nii are poorly defined. Arachidonic acid (AA) and its metabolites are potent mediators of inflammation and have been implicated in host resp onse to microorganisms. We therefore examined the production of eicosa noids from rat and rabbit alveolar macrophages stimulated with Purifie d P. carinii. [C-14]AA-labeled rabbit macrophages released 8.50 +/- 1. 33% of the incorporated [C-14]AA after 90 min in response to P. carini i (P = 0.0001 compared with unstimulated controls). In contrast, a sim ilar number of rat alveolar macrophages exhibited a smaller but signif icant response to P. carinii, releasing 3.84 +/- 1.54% of their [C-14] AA after 90 min (P = 0.001 compared with control). We further determin ed that P carinii stimulated substantial production of prostaglandin E 2 and concurrently a small amount of leukotriene B4 release from alveo lar macrophages. To further investigate whether serum opsonization of P. carinii enhances these alterations in AA metabolism, we assessed th e effect of P. carinii immune serum on P. carinii-induced AA release. P. carinii opsonized with this antiserum caused significantly greater AA release from rat alveolar macrophages than either unopsonized P. ca rinii or organisms opsonized with nonimmune serum. Previous studies su ggest that P carinii interacts with macrophage beta-glucan and mannose receptors. However, incubation of macrophages with P. carinii in the presence of either soluble beta-glucan or alpha-mannan failed to alter the release of AA from macrophages in response to P. carinii. Macroph age release of eicosanoids represents a potentially important host inf lammatory response to P carinii infection.