Diacovo T G, Roth S J, Buccola J M, Bainton D F, Springer T A
Division of Newborn Medicine Harvard Medical School, Boston, MA USA.
Blood. 1996 Jul 1;88(1):146-57.
Platelets bound to thrombogenic surfaces have been shown to support activation-dependent firm adhesion of neutrophils in flow following selectin-mediated tethering and rolling. The specific receptor(s) responsible for mediating adhesion-strengthening interactions between neutrophils and platelets has not previously been identified. Furthermore, the ability of adherent platelets to support the migration of bound neutrophils has not been tested. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte binding in vascular shear flow and emigration at thrombogenic sites. Our results demonstrate that the beta 2-integrin Mac-1 (CD11b/CD18) is required for both firm attachment to and transmigration of neutrophils across surface-adherent platelets. In flow assays, neutrophils from patients with leukocyte adhesion deficiency-1 (LAD-I), which lack beta 2-integrin receptors, formed P-selectin-mediated rolling interactions, but were unable to develop firm adhesion to activated platelets, in contrast to healthy neutrophils, which developed firm adhesion within 5 to 30 seconds after initiation of rolling. Furthermore, the adhesion-strengthening interaction observed for healthy neutrophils could be specifically inhibited by monoclonal antibodies (mAbs) to Mac-1, but not to lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) or intercellular adhesion molecule-2 (ICAM-2; CD102). Further evidence for a beta 2-integrin-dependent neutrophil/platelet interaction is demonstrated by the complete inhibition of interleukin (IL)-8-induced neutrophil transmigration across platelets bound to fibronectin-coated polycarbonate filters by mAbs to Mac-1. Thus, Mac-1 is required for firm adhesion of neutrophils to activated, adherent platelets and may play an important role in promoting neutrophil accumulation on and migration across platelets deposited at sites of vascular injury.
已表明，与血栓形成表面结合的血小板能够在选择素介导的拴系和滚动之后，支持中性粒细胞在流动状态下依赖激活的牢固黏附。此前尚未确定介导中性粒细胞与血小板之间黏附增强相互作用的具体受体。此外，附着的血小板支持结合的中性粒细胞迁移的能力也未得到测试。我们研究了中性粒细胞与活化的、表面附着的血小板之间的相互作用，以此作为血管剪切流中白细胞结合以及在血栓形成部位移出的模型。我们的结果表明，β2整合素Mac-1（CD11b/CD18）对于中性粒细胞牢固附着于表面附着的血小板并穿越它们进行迁移均是必需的。在流动分析中，缺乏β2整合素受体的白细胞黏附缺陷1型（LAD-I）患者的中性粒细胞形成了P选择素介导的滚动相互作用，但与健康中性粒细胞不同，它们无法与活化的血小板形成牢固黏附，健康中性粒细胞在滚动开始后的5至30秒内就形成了牢固黏附。此外，针对Mac-1的单克隆抗体（mAb）可特异性抑制健康中性粒细胞观察到的黏附增强相互作用，但针对淋巴细胞功能相关抗原1（LFA-1；CD11a/CD18）或细胞间黏附分子2（ICAM-2；CD102）的单克隆抗体则不能。针对Mac-1的单克隆抗体完全抑制白细胞介素（IL）-8诱导的中性粒细胞穿越与纤连蛋白包被的聚碳酸酯滤膜结合的血小板的迁移，这进一步证明了β2整合素依赖性中性粒细胞/血小板相互作用。因此，Mac-1是中性粒细胞与活化的、附着的血小板牢固黏附所必需的，并且可能在促进中性粒细胞在血管损伤部位沉积的血小板上的积聚以及穿越血小板迁移中起重要作用。
