Neutrophil priming by cytokines and vitamin D binding protein (Gc-globulin): impact on C5a-mediated chemotaxis, degranulation and respiratory burst
Neutrophil priming by cytokines and vitamin D binding protein (Gc-globulin): impact on C5a-mediated chemotaxis, degranulation and respiratory burst
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DOI：
10.1016/s0161-5890(99)00110-8
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发表时间：
1999-09-01
影响因子：
3.6
通讯作者：
Kirschfink, M
中科院分区：
文献类型：
--
作者：
Binder, R;Kress, A;Kirschfink, M
在急性炎症部位，白细胞面临多种介质，这些介质有望在细胞对单个配体的反应方面相互调节。中性粒细胞以前接触促炎细胞因子，如肿瘤坏死因子-α或粒-巨噬细胞集落刺激因子，或与维生素D结合蛋白(GC-球蛋白)接触，会导致多种或更独特的C5a介导的中性粒细胞功能改变。GC-球蛋白是25-(OH)-D-3的运输蛋白，选择性地作为C5a/C5a(DesArg)的协同趋化因子。相反，先前被证明可以调节FMLP诱导的中性粒细胞反应的肿瘤坏死因子-α和GM-CSF能够降低C5a介导的中性粒细胞的趋化作用，但增强其脱颗粒和呼吸爆发活性。细胞因子刺激伴随着C5a受体(CD88)的下调，而维生素D结合蛋白对中性粒细胞C5a受体水平无影响。C5a本身会减少趋化作用以及脱颗粒和氧化猝发，以应对第二次相同的配体(同源脱敏)。当同一G蛋白偶联的趋化受体亚家族的另一个受体(如FMLP或IL-8的受体)激活时，细胞对给定介质(如对C5a)的反应减弱甚至消失，就会发生类似的效应，称为异源脱敏。与C5a结合，某些分子可能会增强趋化作用，或将中性粒细胞效应功能从迁移转变为胞吐，这是协调炎症反应中一系列事件中的关键步骤。(C)1999爱思唯尔科学有限公司。保留所有权利。
At the site of acute inflammation, leukocytes are confronted with multiple mediators which are expected to modulate each other with respect to cell responses to the individual ligand. Previous contact of neutrophils with pro-inflammatory cytokines, such as TNF-alpha or GM-CSF, or with the vitamin D binding protein (Gc-globulin) leads to the alteration of either multiple or rather distinct C5a-mediated neutrophil functions. Gc-globulin, the transport protein for 25-(OH)-D-3, serves selectively as a cochemotactic factor for C5a/C5a(desArg). In contrast, TNF-alpha and GM-CSF, previously shown to modulate FMLP-induced neutrophil responses, are able to reduce C5a-mediated neutrophil chemotaxis, but augment their degranulation and respiratory burst activity. Cytokine priming was shown to be accompanied by a down-regulation of C5a receptors (CD88) whereas vitamin D binding protein had no impact on the level of neutrophil C5a receptors. C5a itself diminishes chemotaxis as well as degranulation and oxidative burst in response to a second dose of the same ligand (homologous desensitization). A similar effect, termed heterologous desensitization, occurs, if cell responses to a given mediator (e.g. to C5a) are reduced or even abolished upon the activation of another receptor of the same G-protein coupled chemoattractant receptor subfamily (e.g. receptors for FMLP or IL-8). In concert with C5a, certain molecules may either augment chemotaxis or shift neutrophil effector functions from migration to exocytosis, an essential step within the sequence of events in a coordinated inflammatory response. (C) 1999 Elsevier Science Ltd. All rights reserved.