Filler S G, Ibe B O, Ibrahim A S, Ghannoum M A, Raj J U, Edwards J E
Department of Internal Medicine, UCLA School of Medicine.
Infect Immun. 1994 Mar;62(3):1064-9. doi: 10.1128/iai.62.3.1064-1069.1994.
One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.
提高对机会性病原体抵抗力的一种策略是确定入侵过程中的宿主细胞反应，并上调那些与宿主防御机制相关的反应。在此背景下，我们之前已经表明，白色念珠菌在体外侵袭内皮细胞会导致前列腺素生成增加。作为调节内皮细胞前列腺素生成的前提条件，我们现在对这一过程发生的机制进行了表征。白色念珠菌对内皮细胞的侵袭似乎通过上调内皮细胞环氧化酶的合成并增加内皮细胞磷脂酶的活性，刺激花生四烯酸转化为前列腺素。这两种酶活性的增强独立于钙磷蛋白C敏感的蛋白激酶C，并导致前列腺素I2（PGI2）、PGF2α和PGE2的生成增加和细胞外分泌。这些前列腺素的分泌对白色念珠菌诱导的内皮细胞损伤量没有影响。内皮细胞前列腺素分泌增加的作用可能与调节念珠菌 - 白细胞 - 内皮细胞界面处的白细胞反应有关。
