TRANSENDOTHELIAL MIGRATION OF NEUTROPHILS INVOLVES INTEGRIN-ASSOCIATED PROTEIN (CD47)
TRANSENDOTHELIAL MIGRATION OF NEUTROPHILS INVOLVES INTEGRIN-ASSOCIATED PROTEIN (CD47)
复制标题
DOI：
10.1073/pnas.92.9.3978
复制
发表时间：
1995-04-25
影响因子：
11.1
通讯作者：
VADAS, MA
中科院分区：
文献类型：
--
作者：
COOPER, D;LINDBERG, FP;VADAS, MA
炎症是主要的病理过程。炎症反应的发展涉及白色血细胞通过血管内皮衬里进入组织的运动。中性粒细胞的这种跨内皮细胞迁移过程已被证明涉及中性粒细胞β（2）整合素（CD 18）和内皮细胞血小板-内皮细胞粘附分子（PECAM-1; CD 31），我们现在表明抗整合素相关蛋白（IAP）的单克隆抗体B6 H12的F（ab '）（2）片段阻断：由外源性趋化因子白细胞介素8刺激的中性粒细胞的跨内皮迁移（IL-8; 60%抑制），通过趋化肽N-甲酰基-甲硫氨酰亮氨酰苯丙氨酸（FMLP; 76%抑制），或通过细胞因子肿瘤坏死因子α激活内皮（98%抑制）。该抗体有两种作用机制：在中性粒细胞上，它阻止对IL-8和FMLP的趋化反应，在内皮上，它阻止未知但不依赖于IL-8的过程。IAP的阻断抗体不改变内皮细胞粘附蛋白的表达或IL-8的产生，因此对中性粒细胞跨内皮迁移的抑制是选择性的。这些数据表明IAP是中性粒细胞通过内皮细胞迁移到炎症部位所必需的第三种分子。
Inflammation is a primary pathological process. The development of an inflammatory reaction involves the movement of white blood cells through the endothelial lining of blood vessels into tissues, This process of transendothelial cell migration of neutrophils has been shown to involve neutrophil beta(2) integrins (CD18) and endothelial cell platelet-endothelium cell adhesion molecules (PECAM-1; CD31), We now show that F(ab')(2) fragments of the monoclonal antibody B6H12 against integrin-associated protein (IAP) blocks: the transendothelial migration of neutrophils stimulated by an exogenous gradient of the chemokine interleukin 8 (IL-8; 60% inhibition), by the chemotactic peptide N-formyl-methionylleucylphenylalanine (FMLP; 76% inhibition), or by the activation of the endothelium by the cytokine tumor necrosis factor alpha (98% inhibition). The antibody has two mechanisms of action: on neutrophils it prevents the chemotactic response to IL-8 and FMLP, and on endothelium it prevents an unknown but IL-8-independent process. Blocking antibodies to IAP do not alter the expression of adhesion proteins or production of IL-8 by endothelial cells, and thus the inhibition of neutrophil transendothelial migration is selective. These data implicate IAP as the third molecule essential for neutrophil migration through endothelium into sites of inflammation.