Monoclonal antibodies to CD45 modify LPS-induced arachidonic acid metabolism in macrophages
Monoclonal antibodies to CD45 modify LPS-induced arachidonic acid metabolism in macrophages
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DOI：
10.1016/s0167-4889(99)00171-8
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发表时间：
2000-02-28
影响因子：
5.1
通讯作者：
Card, GL
中科院分区：
文献类型：
--
作者：
Pfau, JC;Walker, E;Card, GL
脂多糖（LPS）通过CD 14的信号传导涉及src家族的蛋白酪氨酸激酶的活化，并导致巨噬细胞中细胞因子的产生和花生四烯酸代谢的活化。CD 45蛋白酪氨酸磷酸酶（PTP 4）可能通过这一途径在调节反应中起作用。虽然CD 45在调节T细胞信号传导中的关键作用已被证明，但对其在巨噬细胞中的作用知之甚少。CD 45单克隆抗体和单克隆抗体的F（ab '）（2）片段增强了分化的THP-1单核细胞对LPS的反应，释放放射性标记的花生四烯酸代谢物、前列腺素E-2和肿瘤坏死因子α。通过在有利于CD 14依赖性信号传导的条件下进行实验，显示抗CD 45 mAb的增强作用主要通过该途径发生。此外，LPS可能能够改变CD 45的酶活性，如CD 45免疫沉淀物的Western印迹所示，其中LPS引起CD 45磷酸化状态的瞬时变化。我们的结论是，CD 45似乎通过CD 14途径，可能通过其PTB活性在LPS诱导的反应中发挥作用。(C)2000 Elsevier Science B. V.保留所有权利。
Signaling by lipopolysaccharide (LPS) through CD14 involves the activation of protein tyrosine kinases of the src family and leads to cytokine production and activation of arachidonic acid metabolism in macrophages. CD45 protein tyrosine phosphatase (PTPase) might play a role in modulating the response through this pathway. Although a critical role in regulation of T-cell signaling for CD45 has been demonstrated, little is known about its role in macrophages. Monoclonal antibodies to CD45 and F(ab')(2) fragments of the monoclonal antibody enhanced the response of differentiated THP-1 monocytic cells to LPS for the release of radiolabeled arachidonic acid metabolites, prostaglandin E-2, and tumor necrosis factor alpha. The enhancing effect of anti-CD45 mAbs was shown to occur primarily through CD14-dependent signaling by performing the experiments under conditions favoring that pathway. Further, LPS may be able to alter the enzymatic activity of CD45, as shown by Western blots of CD45 immunoprecipitates in which LPS caused a transient change in the phosphorylation state of CD45. We conclude that CD45 appears to play a role in LPS-induced responses through the CD14 pathway, possibly through its PTPase activity. (C) 2000 Elsevier Science B.V. All rights reserved.