Integrin engagement mediates the human polymorphonuclear leukocyte response to a fungal pathogen-associated molecular pattern
Integrin engagement mediates the human polymorphonuclear leukocyte response to a fungal pathogen-associated molecular pattern
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DOI：
10.4049/jimmunol.178.11.7276
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发表时间：
2007-06-01
影响因子：
4.4
通讯作者：
Reichner, Jonathan S.
中科院分区：
文献类型：
--
作者：
Lavigne, Liz M.;O'Brien, Xian M.;Reichner, Jonathan S.
白细胞从外周血外渗是组织感染部位有效炎症反应所必需的。整合素帮助介导外渗并引导白细胞到达感染源。整合素在调节对真菌病原体细胞壁成分的效应反应中的新作用是当前研究的主题。虽然吞噬作用对清除单细胞真菌是有用的，但对大的、不可食用的菌丝的免疫反应尚不清楚。真菌β -葡聚糖是一种与病原体相关的分子模式，在不需要吞噬的情况下激活白细胞超氧阴离子的产生。为了模拟真菌在不能发生吞噬作用的条件下的多形核白细胞（PMN）识别，将β -葡聚糖共价固定在组织培养塑料上。结果表明，在β -葡聚糖基质中加入β(1)、整合素配体可抑制PMN对固定化β -葡聚糖的氧化爆发反应。抑制是剂量依赖性的，排除了位阻。β(1)整合素配体不影响可摄取的含有β -葡聚糖的颗粒、酚酯或活酵母菌丝的呼吸爆发。此外，在缺乏基质的情况下，Ab激活VLA3或VLA5，而不是其他β(1)整合素，也可以阻止β -葡聚糖诱导的呼吸爆发。通过用可溶性人Fn的细胞结合片段、环状RGD肽或对VLA3或VLA5特异性的Ab处理中性粒细胞，阻断β(1)诱导的抑制，恢复爆发反应。总之，这些发现扩展了β(1)整合素的功能作用，包括将PMN呼吸爆发调节到病原体相关的分子模式。
Extravasation of leukocytes from peripheral blood is required for an effective inflammatory response at sites of tissue infection. Integrins help mediate extravasation and navigate the leukocyte to the infectious source. A novel role for integrins in regulating the effector response to a cell wall component of fungal pathogens is the subject of the current study. Although phagocytosis is useful for clearance of unicellular fungi, the immune response against large, noningestible hyphae is not well-understood. Fungal beta-glucan, a pathogen-associated molecular pattern, activates production of superoxide anion in leukocytes without the need for phagocytosis. To model polymorphonuclear leukocyte (PMN) recognition of fungi under conditions in which phagocytosis cannot occur, beta-glucan was covalently immobilized onto tissue culture plastic. Plasma membrane-associated respiratory burst was measured by reduction of ferricytochrome C. Results show that the human PMN oxidative burst response to immobilized beta-glucan is suppressed by addition of beta(1), integrin ligands to the beta-glucan matrix. Suppression was dose dependent and steric hindrance was ruled out. beta(1) integrin ligands did not affect respiratory burst to ingestible beta-glucan-containing particles, phorbol esters or live yeast hyphae. Furthermore, in the absence of matrix, Ab activation of VLA3 or VLA5, but not other beta(1) integrins, also prevented beta-glucan-induced respiratory burst. beta(1) -induced suppression was blocked and burst response restored by treating neutrophils with either the cell-binding fragment of soluble human Fn, cyclic RGD peptide, or Ab specific to VLA3 or VLA5. Together these findings extend the functional role of beta(1) integrins to include modulating PMN respiratory burst to a pathogen-associated molecular pattern.