Castro M, Morgenthaler T I, Hoffman O A, Standing J E, Rohrbach M S, Limper A H
Thoracic Diseases Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Am J Respir Cell Mol Biol. 1993 Jul;9(1):73-81. doi: 10.1165/ajrcmb/9.1.73.
Pneumocystis carinii is an opportunistic organism that causes severe lung injury in immunocompromised hosts. Macrophage responses to P. carinii are poorly defined. Arachidonic acid (AA) and its metabolites are potent mediators of inflammation and have been implicated in host response to microorganisms. We therefore examined the production of eicosanoids from rat and rabbit alveolar macrophages stimulated with purified P. carinii. [14C]AA-labeled rabbit macrophages released 8.50 +/- 1.33% of the incorporated [14C]AA after 90 min in response to P. carinii (P = 0.0001 compared with unstimulated controls). In contrast, a similar number of rat alveolar macrophages exhibited a smaller but significant response to P. carinii, releasing 3.84 +/- 1.54% of their [14C]AA after 90 min (P = 0.001 compared with control). We further determined that P. carinii stimulated substantial production of prostaglandin E2 and concurrently a small amount of leukotriene B4 release from alveolar macrophages. To further investigate whether serum opsonization of P. carinii enhances these alterations in AA metabolism, we assessed the 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. carinii or organisms opsonized with nonimmune serum. Previous studies suggest 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. Macrophage release of eicosanoids represents a potentially important host inflammatory response to P. carinii infection.
卡氏肺孢子菌是一种机会性致病微生物，可在免疫功能低下的宿主中引起严重的肺损伤。巨噬细胞对卡氏肺孢子菌的反应尚不明确。花生四烯酸（AA）及其代谢产物是炎症的强效介质，并且与宿主对微生物的反应有关。因此，我们检测了用纯化的卡氏肺孢子菌刺激大鼠和兔肺泡巨噬细胞后类花生酸的产生情况。用[14C]AA标记的兔巨噬细胞在受到卡氏肺孢子菌刺激90分钟后，释放了掺入的[14C]AA的8.50±1.33%（与未刺激的对照组相比，P = 0.0001）。相比之下，数量相似的大鼠肺泡巨噬细胞对卡氏肺孢子菌表现出较小但显著的反应，在90分钟后释放了其[14C]AA的3.84±1.54%（与对照组相比，P = 0.001）。我们进一步确定，卡氏肺孢子菌刺激肺泡巨噬细胞大量产生前列腺素E2，同时少量释放白三烯B4。为了进一步研究卡氏肺孢子菌的血清调理作用是否会增强这些AA代谢的改变，我们评估了卡氏肺孢子菌免疫血清对卡氏肺孢子菌诱导的AA释放的影响。用这种抗血清调理的卡氏肺孢子菌比未调理的卡氏肺孢子菌或用非免疫血清调理的微生物从大鼠肺泡巨噬细胞中引起的AA释放显著更多。先前的研究表明，卡氏肺孢子菌与巨噬细胞的β-葡聚糖和甘露糖受体相互作用。然而，在可溶性β-葡聚糖或α-甘露聚糖存在的情况下，将巨噬细胞与卡氏肺孢子菌一起孵育未能改变巨噬细胞对卡氏肺孢子菌反应时AA的释放。巨噬细胞释放类花生酸代表了宿主对卡氏肺孢子菌感染潜在的重要炎症反应。
