Filler S G, Pfunder A S, Spellberg B J, Spellberg J P, Edwards J E
Department of Internal Medicine, St. John's Cardiovascular Research Center, Harbor-UCLA Research and Education Institute, Torrance, California 90509, USA.
Infect Immun. 1996 Jul;64(7):2609-17. doi: 10.1128/iai.64.7.2609-2617.1996.
Endothelial cells have the potential to influence significantly the host immune response to blood-borne microbial pathogens, such as Candida albicans. We investigated the ability (of this organism to stimulate endothelial cell responses relevant to host defense in vitro. Infection with C. albicans induced endothelial cells to express mRNAs encoding E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, interleukin 6, interleukin 8, monocyte chemoattractant protein 1, and inducible cyclooxygenase (cox2). All three leukocyte adhesion molecule proteins were expressed on the surfaces of the endothelial cells after 8 h of exposure to C. albicans. An increase in secretion of all three cytokines was found after 12 h of infection. Cytochalasin D inhibited accumulation of the endothelial cell cytokine and leukocyte adhesion molecule mRNAs in response to C. albicans, suggesting that endothelial cell phagocytosis of the organism is required to induce this response. Live Candida tropicalis, Candida glabrata, a nongerminating strain of C. albicans, and killed C. albicans did not stimulate the expression of any of the cytokine or leukocyte adhesion molecule mRNAs. These findings indicate that a factor associated with live, germinating C. albicans is required for induction of endothelial cell mRNA expression. Furthermore, since endothelial cells phagocytize killed C. albicans, phagocytosis is likely necessary but not sufficient for this organism to stimulate mRNA accumulation. In conclusion, the secretion of proinflammatory cytokines and expression of leukocyte adhesion molecules by endothelial cells in response to C. albicans could enhance the host defense against this organism by contributing to the recruitment of activated leukocytes to sites of intravascular infection.
内皮细胞有潜力显著影响宿主对血源微生物病原体（如白色念珠菌）的免疫反应。我们研究了该生物体在体外刺激与宿主防御相关的内皮细胞反应的能力。白色念珠菌感染诱导内皮细胞表达编码E-选择素、细胞间黏附分子1、血管细胞黏附分子1、白细胞介素6、白细胞介素8、单核细胞趋化蛋白1和诱导型环氧化酶（cox2）的mRNA。暴露于白色念珠菌8小时后，所有三种白细胞黏附分子蛋白均在内皮细胞表面表达。感染12小时后，发现所有三种细胞因子的分泌均增加。细胞松弛素D抑制内皮细胞细胞因子和白细胞黏附分子mRNA因白色念珠菌而积累，这表明该生物体的内皮细胞吞噬作用是诱导这种反应所必需的。活的热带念珠菌、光滑念珠菌、白色念珠菌的非发芽菌株以及灭活的白色念珠菌均未刺激任何细胞因子或白细胞黏附分子mRNA的表达。这些发现表明，诱导内皮细胞mRNA表达需要与活的、发芽的白色念珠菌相关的一个因子。此外，由于内皮细胞吞噬灭活的白色念珠菌，吞噬作用可能是必要的，但不足以使该生物体刺激mRNA积累。总之，内皮细胞对白色念珠菌的反应中促炎细胞因子的分泌和白细胞黏附分子的表达，可通过促进活化白细胞募集到血管内感染部位来增强宿主对该生物体的防御。
