CD11C/CD18 ON NEUTROPHILS RECOGNIZES A DOMAIN AT THE N TERMINUS OF THE A-ALPHA CHAIN OF FIBRINOGEN
CD11C/CD18 ON NEUTROPHILS RECOGNIZES A DOMAIN AT THE N TERMINUS OF THE A-ALPHA CHAIN OF FIBRINOGEN
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DOI：
10.1073/pnas.88.3.1044
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发表时间：
1991-02-01
影响因子：
11.1
通讯作者：
SILVERSTEIN, SC
中科院分区：
文献类型：
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作者：
LOIKE, JD;SODEIK, B;SILVERSTEIN, SC
纤维蛋白原和纤维蛋白充当多种细胞（包括血小板、内皮细胞和白细胞）的粘附基质。 以前，我们确定了纤维蛋白原的γ链的C末端作为纤维蛋白原分子的区域，其包含佛波酯刺激的多形核白细胞上的CD 11b/CD 18（补体受体3）的配体。 与此相反，我们在这里报告，中性粒细胞与肿瘤坏死因子刺激粘附纤维蛋白原包被的表面，但不人血清白蛋白包被的表面，通过整合素CD 11 c/CD 18（p150/95）。 针对CD 11 c/CD 18 α亚基的单克隆抗体LeuM 5和3.9，而不是针对CD 11b/CD 18 α亚基的单克隆抗体OKM 10和OKM 1，可抑制肿瘤坏死因子刺激的中性粒细胞与纤维蛋白原包被表面的粘附。 为了确定由CD 11 c/CD 18识别的纤维蛋白原上的位点，我们研究了肿瘤坏死因子刺激的中性粒细胞与涂覆有各种纤维蛋白原片段的表面的粘附。 受刺激的中性粒细胞粘附于纤维蛋白原N端二硫键结片段或纤维蛋白原E片段包被的表面。 此外，含有序列Gly-Pro-Arg（其对应于纤维蛋白原的A-α链的N-末端区域的氨基酸17-19）的肽和单克隆抗体LeuM 5阻断肿瘤坏死因子刺激的中性粒细胞与纤维蛋白原和纤维蛋白原的N-末端二硫键结片段的粘附。 因此，肿瘤坏死因子刺激的中性粒细胞上的CD 11 c/CD 18作为纤维蛋白原受体发挥功能，其识别纤维蛋白原A-α链N-末端结构域中的序列Gly-Pro-Arg。
Fibrinogen and fibrin serve as adhesive substrates for a variety of cells including platelets, endothelial cells, and leukocytes. Previously, we identified the C terminus of the gamma-chain of fibrinogen as the region of the fibrinogen molecule that contains a ligand for CD11b/CD18 (complement receptor 3) on phorbol ester-stimulated polymorphonuclear leukocytes. In contrast, we report here that neutrophils stimulated with tumor necrosis factor adhere to fibrinogen-coated surfaces, but not to human serum albumin-coated surfaces, via the integrin CD11c/CD18 (p150/95). Monoclonal antibodies LeuM5 and 3.9, which are directed against the alpha subunit of CD11c/CD18, but not monoclonal antibodies OKM10 and OKM1, which are directed against the alpha subunit of CD11b/CD18, inhibit the adhesion of tumor necrosis factor-stimulated neutrophils to fibrinogen-coated surfaces. To identify the site on fibrinogen recognized by CD11c/CD18, we have examined the adhesion of tumor necrosis factor-stimulated neutrophils to surfaces coated with various fibrinogen fragments. Stimulated neutrophils adhere to surfaces coated with the N-terminal disulfide knot fragment of fibrinogen or fibrinogen fragment E. Moreover, peptides containing the sequence Gly-Pro-Arg (which corresponds to amino acids 17-19 of the N-terminal region of the A-alpha chain of fibrinogen), and monoclonal antibody LeuM5, block tumor necrosis factor-stimulated neutrophil adhesion to fibrinogen and to the N-terminal disulfide knot fragment of fibrinogen. Thus, CD11c/CD18 on tumor necrosis factor-stimulated neutrophils functions as a fibrinogen receptor that recognizes the sequence Gly-Pro-Arg in the N-terminal domain of the A-alpha chain of fibrinogen.