Neutrophil-derived resistin release induced by Aggregatibacter actinomycetemcomitans
Neutrophil-derived resistin release induced by Aggregatibacter actinomycetemcomitans
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DOI：
10.1111/j.1574-6968.2011.02334.x
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发表时间：
2011-08-01
影响因子：
2.1
通讯作者：
Saito, Toshiyuki
中科院分区：
文献类型：
--
作者：
Furugen, Reiko;Hayashida, Hideaki;Saito, Toshiyuki
抵抗素是一种诱导小鼠胰岛素抵抗的脂肪因子。在人类中，抵抗素不是在脂肪细胞中产生的，而是在各种白细胞中产生的，它是一种促炎分子。目前的研究表明，高水平的抵抗素在中性粒细胞的培养上清液中被高白细胞毒性的放线菌聚集菌刺激。相反，当中性粒细胞暴露于另外两种产生最低水平白质毒素的菌株和另一种不能产生白质毒素的等基因突变菌株时，抵抗素的水平非常低。在与高白细胞毒性菌株孵育前，用CD18单克隆抗体、β链淋巴细胞功能相关分子1 （LFA-1）或Src家族酪氨酸激酶抑制剂预处理中性粒细胞可抑制抵抗素的释放。这些结果表明，A. actinomycetemcomitans表达的白毒素通过与中性粒细胞表面的LFA-1相互作用诱导人中性粒细胞来源的抵抗素的细胞外释放，从而激活Src家族酪氨酸激酶。
Resistin is an adipokine that induces insulin resistance in mice. In humans, resistin is not produced in adipocytes, but in various leukocytes instead, and it acts as a proinflammatory molecule. The present investigation demonstrated high levels of resistin in culture supernatants of neutrophils that are stimulated by a highly leukotoxic strain of Aggregatibacter actinomycetemcomitans. In contrast, the level of resistin was remarkably low when neutrophils were exposed to two other strains that produce minimal levels of leukotoxin and a further isogenic mutant strain incapable of producing leukotoxin. Pretreatment of neutrophils with a monoclonal antibody to CD18, beta chain of lymphocyte function-associated molecule 1 (LFA-1), or an Src family tyrosine kinase inhibitor before incubation with the highly leukotoxic strain inhibited the release of resistin. These results show that A. actinomycetemcomitans-expressed leukotoxin induces extracellular release of human neutrophil-derived resistin by interacting with LFA-1 on the surface of neutrophils and, consequently, activating Src family tyrosine kinases.