Complement receptor 3 (CR3, Mac-1, integrin alpha M beta 2, CD11b/CD18) is required for tyrosine phosphorylation of paxillin in adherent and nonadherent neutrophils.
Complement receptor 3 (CR3, Mac-1, integrin alpha M beta 2, CD11b/CD18) is required for tyrosine phosphorylation of paxillin in adherent and nonadherent neutrophils.
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DOI：
10.1083/jcb.127.4.1139
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发表时间：
1994-11
影响因子：
7.8
通讯作者：
Brown, E J
中科院分区：
文献类型：
--
作者：
Graham, I L;Anderson, D C;Holers, V M;Brown, E J
白细胞（β 2）整联蛋白的表达是活化的中性粒细胞（PMN）的许多功能所必需的，即使在没有任何β 2整联蛋白的识别配体时也是如此。为了研究β 2整合素可能参与细胞骨架重组相关的信号转导途径的假设，我们研究了β 2整合素是否在细胞骨架蛋白桩蛋白的酪氨酸磷酸化中起作用。用佛波醇酯、f-Met-Leu-Phe和TNF-α处理悬浮液中的PMN导致桩蛋白酪氨酸磷酸化。然而，治疗β 2-缺陷（LAD）PMN未能诱导桩蛋白酪氨酸磷酸化。正常PMN磷酸化桩蛋白的免疫复合物的粘附，而LAD PMN没有。佛波酯激活的LAD中性粒细胞的细胞外基质蛋白纤连蛋白，层粘连蛋白，玻连蛋白的粘附未能诱导桩蛋白酪氨酸磷酸化。用针对β 2整联蛋白α链的mAb处理活化的正常PMN证明CR 3（α M β 2）是桩蛋白磷酸化所需的。用CR 3转染细胞系K562证实CR 3连接导致桩蛋白酪氨酸磷酸化。作为对照，用CR2（CD 21）转染的K562在受体连接后未显示增强的桩蛋白酪氨酸磷酸化，所述CR2（CD 21）与CR 3转染子同样地结合至相同的补体C3衍生配体（C3 bi）。虽然CR2和CR 3转染子都显示出对C3 bi包被的表面的有效粘附，但只有CR 3转染子在粘附和磷酸化桩蛋白期间扩散。总之，这些数据表明，CR 3是所需的桩蛋白磷酸化过程中的粘附和非粘附PMN。即使PMN在悬浮液中或通过粘附于免疫复合物而活化，当没有CR 3配体时，仍然需要CR 3用于导致桩蛋白酪氨酸磷酸化的信号转导途径。该通路可能对PMN在炎症和宿主防御中的功能很重要。
Expression of the leukocyte (beta 2) integrins is required for many functions of activated neutrophils (PMN), even when there is no recognized ligand for any beta 2 integrin. To investigate the hypothesis that beta 2 integrins may be involved in a signal transduction pathway related to cytoskeletal reorganization, we examined whether beta 2 integrins have a role in tyrosine phosphorylation of the cytoskeletal protein paxillin. Treatment of PMN in suspension with phorbol esters, f-Met-Leu-Phe, and TNF-alpha resulted in paxillin tyrosine phosphorylation. However, treatment of beta 2-deficient (LAD) PMN failed to induce paxillin tyrosine phosphorylation. Normal PMN phosphorylated paxillin in response to adhesion to immune complexes, while the LAD PMN did not. Adhesion of phorbol ester activated-LAD PMN to the extracellular matrix proteins fibronectin, laminin, and vitronectin failed to induce paxillin tyrosine phosphorylation. Treatment of activated normal PMN with mAb directed against the beta 2 integrin alpha chains demonstrated that CR3 (alpha M beta 2) was required for paxillin phosphorylation. Transfection of the cell line K562 with CR3 confirmed that CR3 ligation resulted in paxillin tyrosine phosphorylation. As a control, K562 transfected with CR2 (CD21) which bound equally avidly to the same complement C3-derived ligand (C3bi) as the CR3 transfectants, showed no enhanced tyrosine phosphorylation of paxillin upon receptor ligation. While both CR2 and CR3 transfectants showed efficient adhesion to a C3bi-coated surface, only the CR3 transfectants spread during adhesion and phosphorylated paxillin. Together these data demonstrate that CR3 is required for paxillin phosphorylation during activation of both adherent and nonadherent PMN. Even PMN activated in suspension or by adhesion to immune complexes, when no CR3 ligand is apparent, still require CR3 for a signal transduction pathway leading to paxillin tyrosine phosphorylation. This pathway is likely to be important for PMN function in inflammation and host defense.