Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen.
Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen.
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DOI：
10.1073/pnas.85.20.7734
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发表时间：
1988-10
影响因子：
11.1
通讯作者：
S. D. Wright;Jeffrey I. Weitz;A. J. Huang;S. Levin;Samuel C. Silverstein;J. Loike
中科院分区：
文献类型：
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作者：
S. D. Wright;Jeffrey I. Weitz;A. J. Huang;S. Levin;Samuel C. Silverstein;J. Loike
人类多形核白细胞（PMN）先前已被证明与纤维蛋白聚集体和纤维蛋白原包被的表面结合。在与纤维蛋白原包被的表面相互作用过程中，PMN与表面紧密接触，使得部分分泌的弹性酶活性不受周围介质中大分子蛋白酶抑制剂的影响。本研究表明，PMN上介导这种相互作用的受体是补体受体3型（CR3; CD11b/CD18），该分子先前被鉴定为补体蛋白片段C3bi的受体。抗CR3的单克隆抗体阻断C3bi的结合，也阻断PMN与纤维蛋白原包被表面的结合和保护隔室的形成。CR3识别的纤维蛋白原区域位于γ链的羧基端，因为基于该序列的肽有效地抑制PMN与纤维蛋白原包被表面的结合。这些肽也阻断C3bi包被红细胞与CR3的结合，从而表明单个结合位点用于结合C3bi和纤维蛋白原。序列分析表明，该纤维蛋白原区域与其他已知的CR3配体具有很强的结构相似性。这些研究表明，CR3不仅是C3bi的受体，也是纤维蛋白原的受体。
Human polymorphonuclear leukocytes (PMN) have previously been shown to bind to aggregates of fibrin and to fibrinogen-coated surfaces. During their interactions with fibrinogen-coated surfaces, PMN make such close contact with the surface that a portion of the secreted elastase activity is protected from macromolecular protease inhibitors in the surrounding medium. Here we show that the receptor on PMN that mediates this interaction is complement receptor type 3 (CR3; CD11b/CD18), a molecule previously identified as a receptor for the complement protein fragment C3bi. Monoclonal antibodies against CR3 that block the binding of C3bi also block the binding of PMN to fibrinogen-coated surfaces and the formation of a protected compartment. The region of fibrinogen recognized by CR3 lies at the carboxyl terminus of the gamma chain, since peptides based on this sequence effectively inhibit the binding of PMN to fibrinogen-coated surfaces. These peptides also block the binding of C3bi-coated erythrocytes to CR3, thus indicating that a single binding site is used for binding both C3bi and fibrinogen. Sequence analysis shows strong structural similarity between this region of fibrinogen and other known ligands of CR3. These studies thus indicate that CR3 functions as a receptor not only for C3bi but also for fibrinogen.