Circulating platelet-neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing

Circulating platelet-neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing
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DOI:
10.1046/j.1365-2141.1999.01553.x
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发表时间:
1999-08-01
影响因子:
6.5
通讯作者:
Klein, NJ
Klein, NJ
中科院分区:
医学2区
文献类型:
--
作者:
Peters, MJ;Dixon, G;Klein, NJ

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血小板在连接炎症、止血和血栓形成过程中起着重要作用。最近的研究表明,血小板通过血小板CD 62 β和白细胞β 2整合素与白细胞形成异型聚集体。这些相互作用已被观察到在体外从健康志愿者的血液和在临床条件下,血栓形成和炎症是prominent.This研究的血小板-中性粒细胞复合物(PNC)在抗凝全血的属性。在静息状态下,PNC中的中性粒细胞比游离中性粒细胞表现出显著更多的活化粘附分子谱,CD 11b表达和活化增加(CD 11b/CD 18“活化报告基因”单克隆抗体24的结合增加),CD 62 L表达降低。此外,PNCs中的中性粒细胞吞噬脑膜炎奈瑟菌的能力显著高于游离中性粒细胞,并产生更多的有毒氧代谢产物,血小板激动剂二磷酸腺苷(ADP)刺激导致整个中性粒细胞群体中CD 11b表达和活化进一步增加,CD 62 L丢失以及吞噬作用和有毒氧代谢产物产生增加。当用CD 62 P阻断抗体G1重复这些实验时,根据所研究的参数,效应受到不同程度的抑制。这些结果表明,可溶性和接触依赖性因素有助于血小板介导的中性粒细胞activation.Platelet中性粒细胞复合物代表了一个更活跃的粘附分子配置文件,并具有更大的吞噬能力和有毒的氧代谢产物的中性粒细胞的大的亚群。这项研究为PNC在健康和疾病中的作用提供了进一步的支持。
Platelets play a prominent role in linking the processes of inflammation haemostasis and thrombosis. Recent studies have shown that platelets form heterotypic aggregates with leucocytes via platelet CD62P and leucocyte beta 2 integrins. These interactions have been observed in vitro in blood taken from healthy volunteers and in clinical conditions in which thrombosis and inflammation are prominent.This study investigated the properties of platelet-neutrophil complexes (PNCs) in anticoagulated whole blood. At rest, neutrophils in PNCs exhibit a significantly more activated adhesion molecule profile than free neutrophils with increased CD11b expression and activation (increased binding of the CD11b/CD18 'activation reporter' monoclonal antibody 24) and decreased CD62L expression. In addition, neutrophils in PNCs phagocytosed significantly more Neisseria meningitidis and produced more toxic oxygen metabolites than free neutrophils.Stimulation with the platelet agonist adenosine diphosphate (ADP) led to further increases in CD11b expression and activation, loss of CD62L as well as increased phagocytosis and toxic oxygen metabolite production throughout the whole neutrophil population. When these experiments were repeated with the CD62P blocking antibody G1 the effects were inhibited to a variable extent, dependent upon the parameter under investigation. These results indicate that both soluble and contact-dependent factors contribute to platelet-mediated neutrophil activation.Platelet neutrophil complexes represent a large subpopulation of neutrophils with a more activated adhesion molecule profile, and a greater capacity for phagocytosis and toxic oxygen metabolite production. This study provides further support for a role for PNCs in both health and disease.