CHEMOTACTIC FACTORS REGULATE LECTIN ADHESION MOLECULE 1 (LECAM-1)-DEPENDENT NEUTROPHIL ADHESION TO CYTOKINE-STIMULATED ENDOTHELIAL-CELLS INVITRO
CHEMOTACTIC FACTORS REGULATE LECTIN ADHESION MOLECULE 1 (LECAM-1)-DEPENDENT NEUTROPHIL ADHESION TO CYTOKINE-STIMULATED ENDOTHELIAL-CELLS INVITRO
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DOI：
10.1172/jci115037
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发表时间：
1991-02-01
影响因子：
15.9
通讯作者：
ANDERSON, DC
中科院分区：
文献类型：
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作者：
SMITH, CW;KISHIMOTO, TK;ANDERSON, DC
使用识别 CD18、CD11a、CD11b 和中性粒细胞凝集素粘附分子 1 (LECAM-1)（即鼠 MEL-14 抗原的人类同源物）的单克隆抗体来评估这些糖蛋白对中性粒细胞内皮粘附的相对贡献。 在静态条件下，中性粒细胞与IL-1刺激的人脐静脉内皮细胞（HUVEC）单层的粘附被CD18、CD11a和中性粒细胞LECAM-1抗体抑制，并且抗LECAM-1和抗CD11a组合的效果几乎是相加的。 在壁剪切应力为 1.85 dyn/cm2 的流动下（CD18 依赖性粘附力最小的情况），抗 LECAM-1 抑制粘附力 > 50%。中性粒细胞的趋化刺激导致中性粒细胞中的LECAM-1快速丢失，导致中性粒细胞表面的LECAM-1快速丢失，并且中性粒细胞表面LECAM-1的水平与流动下的粘附密切相关。 接触活化内皮细胞30分钟的中性粒细胞失去了大部分表面LECAM-1，这是由受刺激的单层释放到培养基中的可溶性因子或多种因子诱导的现象，并且高百分比迁移通过HUVEC单层。 这种迁移几乎完全被抗 CD18 抑制，但不受中性粒细胞 LECAM-1 抗体的影响。 这些结果支持这样的概念：LECAM-1是一种中性粒细胞粘附分子，在流动条件下参与未刺激的中性粒细胞与细胞因子刺激的内皮细胞的粘附，然后从中性粒细胞表面丢失，同时与导致跨内皮迁移的CD18依赖性机制的结合相一致。
Monoclonal antibodies recognizing CD18, CD11a, CD11b, and neutrophil lectin adhesion molecule 1 (LECAM-1), i.e., the human homologue of the murine MEL-14 antigen, were used to assess the relative contribution of these glycoproteins to neutrophil-endothelial adhesion. Under static conditions, the adhesion of neutrophils to IL-1-stimulated human umbilical vein endothelial cell (HUVEC) monolayers was inhibited by antibodies to CD18, CD11a, and the neutrophil LECAM-1, and the effect of combining anti-LECAM-1 and anti-CD11a was almost additive. Under flow at a wall shear stress of 1.85 dyn/cm2, a condition where CD18-dependent adhesion is minimal, anti-LECAM-1 inhibited adhesion by > 50%. Chemotactic stimulation of neutrophils induced a rapid loss of LECAM-1 from the neutrophils induced a rapid loss of LECAM-1 from the neutrophil surface, and the level of neutrophil surface LECAM-1 was closely correlated with adhesion under flow. Neutrophils contacting the activated endothelial cells for 30 min lost most of their surface LECAM-1, a phenomenon induced by a soluble factor or factors released into the medium by the stimulated monolayers, and a high percentage migrated through the HUVEC monolayer. This migration was almost completely inhibited by anti-CD18, but was unaffected by antibodies to neutrophil LECAM-1. These results support the concept that LECAM-1 is a neutrophil adhesion molecule that participates in the adherence of unstimulated neutrophils to cytokine-stimulated endothelial cells under conditions of flow, and is then lost from the neutrophil surface coincident with the engagement of CD18-dependent mechanisms leading to transendothelial migration.