Blanks J E, Moll T, Eytner R, Vestweber D
Institute of Cell Biology, ZMBE, University of Münster, Germany.
Eur J Immunol. 1998 Feb;28(2):433-43. doi: 10.1002/(SICI)1521-4141(199802)28:02<433::AID-IMMU433>3.0.CO;2-U.
The entry of neutrophils into inflamed tissues is initiated by cell rolling on the blood vessel wall followed by arrest and transendothelial migration. Rolling is mediated by the selectins, while the two subsequent steps require activated beta 2-integrins. We have investigated whether the binding of P-selectin to mouse neutrophils could trigger the activation of beta 2-integrins. We show that cross-linking of P-selectin glycoprotein ligand-1 (PSGL-1) on mouse neutrophils with an antibody-like recombinant form of P-selectin or with monoclonal antibodies stimulated the production of reactive oxygen intermediates and enhanced neutrophil attachment to intercellular adhesion molecule 1 (ICAM-1)-expressing CHO cells. This effect was independent of whether complete antibodies or F(ab')2 fragments were used. The adhesion-stimulating effect of P-selectin could be blocked by monoclonal antibodies against PSGL-1. Increase of cell attachment was dependent on lymphocyte function-associated antigen 1 (LFA-1) and on Mac-1, since it could be blocked with antibodies against both respective integrin alpha-chains. Moreover, cell surface expression of Mac-1 increased upon cross-linking of PSGL-1. In agreement with published data, treatment of human neutrophils with P-selectin-IgG did not enhance attachment to ICAM-1. Our data suggest that ligation of PSGL-1 on mouse neutrophils, but not on human neutrophils, activates beta 2-integrin mediated cell attachment to ICAM-1.
中性粒细胞进入炎症组织始于在血管壁上滚动，随后发生停滞并进行跨内皮迁移。滚动由选择素介导，而随后的两个步骤需要激活的β2整合素。我们研究了P选择素与小鼠中性粒细胞的结合是否能触发β2整合素的激活。我们发现，用抗体样重组形式的P选择素或单克隆抗体使小鼠中性粒细胞上的P选择素糖蛋白配体-1（PSGL-1）交联，可刺激活性氧中间体的产生，并增强中性粒细胞与表达细胞间黏附分子1（ICAM-1）的CHO细胞的黏附。这种效应与使用完整抗体还是F(ab')2片段无关。P选择素的黏附刺激作用可被抗PSGL-1的单克隆抗体阻断。细胞黏附的增加依赖于淋巴细胞功能相关抗原1（LFA-1）和Mac-1，因为它可被针对各自整合素α链的抗体阻断。此外，PSGL-1交联后Mac-1的细胞表面表达增加。与已发表的数据一致，用P选择素-IgG处理人中性粒细胞不会增强其与ICAM-1的黏附。我们的数据表明，小鼠中性粒细胞而非人中性粒细胞上PSGL-1的连接激活了β2整合素介导的细胞与ICAM-1的黏附。
