<br>Mac-1 (CDIIb/CD18) 在体内免疫复合物刺激中性粒细胞功能中的作用：Mac-1 缺乏会消除急性肾小球肾炎中持续的 Fcgamma 受体依赖性中性粒细胞粘附和补体依赖性蛋白尿。,Journal of Experimental Medicine

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Mac-1 (CDIIb/CD18) 在体内免疫复合物刺激中性粒细胞功能中的作用：Mac-1 缺乏会消除急性肾小球肾炎中持续的 Fcgamma 受体依赖性中性粒细胞粘附和补体依赖性蛋白尿。
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 1997-12-01 , DOI: 10.1084/jem.186.11.1853
T Tang ₁ , A Rosenkranz , K J Assmann , M J Goodman , J C Gutierrez-Ramos , M C Carroll , R S Cotran , T N Mayadas

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Mac-1 (alphambeta2) 是一种白细胞粘附受体，在体外已被证明可以与 Fcgamma 受体发生功能性相互作用，以促进免疫复合物 (IC) 刺激的多形核中性粒细胞 (PMN) 功能。为了研究Mac-1-FcgammaR相互作用在IC介导的体内损伤中的相关性，我们通过静脉注射在野生型和Mac-1缺陷型小鼠中诱导了Fc依赖性抗肾小球基底膜（GBM）肾炎模型注射抗GBM抗体。 Mac-1 无效小鼠和野生型小鼠中最初肾小球 PMN 积累相当，但此后野生型小鼠中增加，突变型小鼠中减少。 Mac-1 与明显配体、细胞间粘附分子 1 (ICAM-1) 和 C3 补体相互作用的缺乏，并不是 Mac-1 缺陷小鼠中中性粒细胞积累减少的原因，因为这些缺陷小鼠中的肾小球 PMN 积累配体与野生型小鼠的配体相当。体外研究表明，Mac-1-null PMN 在 5-12 分钟时向 IC 包被的培养皿中的扩散与野生型 PMN 的扩散相当，但此后明显减少，并且与突变型中性粒细胞无法重新分布丝状细胞有关。肌动蛋白。这表明在体内，Mac-1 不是 Fc 介导的 PMN 募集启动所必需的，但丝状肌动蛋白重组需要 Mac-1-FcgammaR 相互作用，从而导致持续的 PMN 粘附，这代表了相关性的首次证明Mac-1-FcgammaR 体内相互作用的研究。 PMN 依赖性蛋白尿在野生型小鼠中在 8 小时时达到最大值，而在 Mac-1 突变型小鼠中在所有时间点均不存在。与野生型小鼠相比，补体 C3 缺陷小鼠的蛋白尿也显着降低。由于 PMN 上的 Mac-1 是 ic3b 的主要配体，因此 Mac-1 与 C3 相互作用的缺失可能有助于消除 Mac-1 缺失小鼠的蛋白尿。

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A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis.

Mac-1 (alphambeta2), a leukocyte adhesion receptor, has been shown in vitro to functionally interact with Fcgamma receptors to facilitate immune complex (IC)-stimulated polymorphonuclear neutrophil (PMN) functions. To investigate the relevance of Mac-1-FcgammaR interactions in IC-mediated injury in vivo, we induced a model of Fc-dependent anti-glomerular basement membrane (GBM) nephritis in wild-type and Mac-1-deficient mice by the intravenous injection of anti-GBM antibody. The initial glomerular PMN accumulation was equivalent in Mac-1 null and wild-type mice, but thereafter increased in wild-type and decreased in mutant mice. The absence of Mac-1 interactions with obvious ligands, intercellular adhesion molecule 1 (ICAM-1), and C3 complement, is not responsible for the decrease in neutrophil accumulation in Mac-1- deficient mice since glomerular PMN accumulation in mice deficient in these ligands was comparable to those in wild-type mice. In vitro studies showed that spreading of Mac-1-null PMNs to IC-coated dishes was equivalent to that of wild-type PMNs at 5-12 min but was markedly reduced thereafter, and was associated with an inability of mutant neutrophils to redistribute filamentous actin. This suggests that in vivo, Mac-1 is not required for the initiation of Fc-mediated PMN recruitment but that Mac-1-FcgammaR interactions are required for filamentous actin reorganization leading to sustained PMN adhesion, and this represents the first demonstration of the relevance of Mac-1-FcgammaR interactions in vivo. PMN-dependent proteinuria, maximal in wild-type mice at 8 h, was absent in Mac-1 mutant mice at all time points. Complement C3-deficient mice also had significantly decreased proteinuria compared to wild-type mice. Since Mac-1 on PMNs is the principal ligand for ic3b, an absence of Mac-1 interaction with C3 probably contributed to the abrogation of proteinuria in Mac-1-null mice.

更新日期：2019-11-01

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