Interactions of Aspergillus fumigatus with endothelial cells:: internalization, injury, and stimulation of tissue factor activity
Interactions of Aspergillus fumigatus with endothelial cells:: internalization, injury, and stimulation of tissue factor activity
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DOI：
10.1182/blood-2003-06-2186
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发表时间：
2004-03-15
期刊：
影响因子：
20.3
通讯作者：
Filler, SG
中科院分区：
文献类型：
--
作者：
Bezerra, LML;Filler, SG
侵袭性曲霉菌病导致血液系统恶性肿瘤患者显著死亡。这种感染的特征是血管侵犯和血栓形成。为了研究侵袭性曲霉病的发病机制，我们在体外研究了烟曲霉分生孢子和菌丝与内皮细胞的相互作用。我们发现，这两种形式的有机体诱导内皮细胞微丝重排和随后的内吞作用。分生孢子被内吞2倍以上的贪婪比菌丝，内吞是独立的真菌活力。感染4小时后，内吞的分生孢子和菌丝引起进行性内皮细胞损伤。活分生孢子比活菌丝诱导更多的内皮细胞损伤。然而，由分生孢子引起的内皮细胞损伤依赖于真菌的活力，而由菌丝引起的损伤则不依赖于真菌的活力，这表明分生孢子和菌丝通过不同的机制损伤内皮细胞。无论是活的还是死的分生孢子都不增加内皮细胞的组织因子活性。与此相反，活的和杀死的菌丝刺激显着的内皮细胞组织因子活性，以及组织因子抗原在内皮细胞表面上的表达。这些结果表明，在体内由烟曲霉菌丝引起的血管侵袭和血栓形成可能部分是由于内皮细胞侵袭，诱导损伤，和刺激组织因子活性。(C)2004年，美国血液学会。
Invasive aspergillosis causes significant mortality among patients with hematologic malignancies. This infection is characterized by vascular invasion and thrombosis. To study the pathogenesis of invasive aspergillosis, we investigated the interactions of Aspergillus fumigatus conidia and hyphae with endothelial cells in vitro. We found that both forms of the organism induced endothelial cell microfilament rearrangement and subsequent endocytosis. Conidia were endocytosed 2-fold more avidly than hyphae, and endocytosis was independent of fungal viability. Endocytosed conidia and hyphae caused progressive endothelial cell injury after 4 hours of infection. Live conidia induced more endothelial cell injury than did live hyphae. However, endothelial cell injury caused by conidia was dependent on fungal viability, whereas injury caused by hyphae was not, indicating that conidia and hyphae injure endothelial cells by different mechanisms. Neither live nor killed conidia increased tissue factor activity of endothelial cells. In contrast, both live and killed hyphae stimulated significant endothelial cell tissue factor activity, as well as the expression of tissue factor antigen on the endothelial cell surface. These results suggest that angioinvasion and thrombosis caused by A fumigatus hyphae in vivo may be due in part to endothelial cell invasion, induction of injury, and stimulation of tissue factor activity. (C) 2004 by The American Society of Hematology.