Platelet factor 4-induced neutrophil-endothelial cell interaction: involvement of mechanisms and functional consequences different from those elicited by interleukin-8.
Platelet factor 4-induced neutrophil-endothelial cell interaction: involvement of mechanisms and functional consequences different from those elicited by interleukin-8.
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DOI：
10.1182/blood.v94.12.4020.424k03_4020_4028
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发表时间：
1999-12
期刊：
影响因子：
20.3
通讯作者：
F. Petersen;L. Bock;H. Flad;E. Brandt
中科院分区：
文献类型：
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作者：
F. Petersen;L. Bock;H. Flad;E. Brandt
血小板因子4（PF-4）是趋化因子CXC亚家族的成员，由活化的血小板大量分泌。在以前的研究中，我们发现PF-4特异性结合人多形粒细胞（PMN），但需要肿瘤坏死因子-α（TNF-α）作为共刺激诱导悬浮细胞中的效应功能。在本研究中，我们研究了PF-4与白细胞介素-8（IL-8）相比，其促进PMN与培养的内皮细胞（EC）相互作用的能力。我们在这里首次表明，PF-4剂量依赖性诱导中性粒细胞进行非常坚定的粘附EC以及exocytose二级颗粒内容物在这些细胞的存在下。有趣的是，不需要TNF-α的共刺激，表明EC可以提供相应的信号。从抗体阻断实验中可以看出，PF-4诱导的粘附涉及PMN表达的L-选择素以及白细胞功能相关分子-1（LFA-1），而IL-8涉及MAC-1。由于阻断LFA-1抗体而不是L-选择素或MAC-1废除PF-4依赖性标记物从PMN胞吐，EC提供的共刺激信号似乎是通过LFA-1引起的细胞-细胞接触。诱导MAC-1上调的IL-8在与EC接触时不引起标记物胞吐。我们的研究结果表明PF-4在促进PMN-EC相互作用中的作用与其他CXC趋化因子如IL-8所表现出的作用几乎不同。
Platelet factor 4 (PF-4), a member of the CXC-subfamily of chemokines, is secreted in high amounts by activated platelets. In previous studies, we found that PF-4 specifically binds to human polymorphonuclear granulocytes (PMN), but requires tumor necrosis factor-alpha (TNF-alpha) as a costimulus for the induction of effector functions in suspended cells. In the present study, we have examined PF-4 in comparison with interleukin-8 (IL-8) for its ability to promote interaction of PMN with cultured endothelial cells (EC). We show here for the first time that PF-4 dose-dependently induces PMN to undergo extremely firm adhesion to EC as well as to exocytose secondary granule contents in the presence of these cells. Interestingly, costimulation by TNF-alpha was not required, indicating that EC could provide a corresponding signal(s). As evident from antibody blocking experiments, PF-4-induced adhesion involved PMN-expressed L-selectin as well as leukocyte function-associated molecule-1 (LFA-1), whereas IL-8 involved MAC-1. Because blocking antibodies to LFA-1 but not to L-selectin or MAC-1 abrogated PF-4-dependent marker exocytosis from PMN, the costimulatory signal provided by EC appears to be elicited through cell-cell contact via LFA-1. IL-8, inducing the upregulation of MAC-1, did not elicit marker exocytosis in contact with EC. Our results suggest a role for PF-4 in the promotion of PMN-EC interaction that is virtually different from that exhibited by other CXC-chemokines such as IL-8.