Abstract
Surface receptor-mediated adhesion is a fundamental step in the recruitment of leukocytes and platelets, as well as platelet–leukocyte interactions. The surface receptor CD147 is crucially involved in host defense against self-derived and invading targets, as well as in thrombosis. In the current study, we describe the previously unknown interaction of CD147 with integrin αMβ2 (Mac-1) in this context. Using binding assays, we were able to show a stable interaction of CD147 with Mac-1 in vitro. Leukocytes from Mac-1−/− and CD147+/− mice showed a markedly reduced static adhesion to CD147- and Mac-1-coated surfaces, respectively, compared to wild-type mice. Similarly, we observed reduced rolling and adhesion of monocytes under flow conditions when cells were pre-treated with antibodies against Mac-1 or CD147. Additionally, as assessed by antibody inhibition experiments, CD147 mediated the dynamic adhesion of platelets to Mac-1-coated surfaces. The interaction of CD147 with Mac-1 is a previously undescribed mechanism facilitating the adhesion of leukocytes and platelets.
Highlights
The recruitment of leukocytes and platelets to activated endothelium as well as platelet-leukocyte interactions are of fundamental significance for innate and adaptive immunity, as well as thrombosis [1]
The surface receptor CD147 has been shown to be important in the host defense from self-derived as well as invading targets and is a major factor regulating the expression of matrix metalloproteinases (MMPs)
Our group identified glycoprotein VI (GPVI) to be an adhesion-mediating partner for CD147 on the platelet surface, which is the first time it has been demonstrated that CD147 plays a direct role in cell adhesive events, apart from mediating adhesion via intracellular signaling, leading to the expression of adhesion molecules [11]
Summary
The recruitment of leukocytes and platelets to activated endothelium as well as platelet-leukocyte interactions are of fundamental significance for innate and adaptive immunity, as well as thrombosis [1]. CD147 is a pathophysiologically important multi-ligand receptor of the immunoglobulin superfamily It is expressed in various tissues and cell types, including leukocytes, endothelial cells, and platelets. In the context of thromboinflammation, CD147 acts as a pro-inflammatory and pro-thrombotic receptor, eliciting leukocyte chemotaxis and adhesion, as well as platelet activation and subsequent thrombus formation through the binding of various interaction partners [4,7,8,9,10,11,12]. On neutrophils, Mac-1 plays an important role in adhesion to the endothelium upon activation [18,19,20] In this context, Mac-1-dependent adhesive interactions enable the cells to crawl on the surface of endothelial cells prior to extravasation [16,21]. We provide evidence that CD147 is a novel and relevant binding partner for Mac-1 on leukocytes and platelets
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