抗CD14抗体IC14对人内毒素血症期间血浆和细胞相关趋化因子的影响。

Effect of IC14, an anti-CD14 antibody, on plasma and cell-associated chemokines during human endotoxemia.

作者信息

Olszyna Dariusz P, Verbon Annelies, Pribble John P, Turner Terence, Axtelle Tim, van Deventer Sander J H, van der Poll Tom

机构信息

Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

出版信息

Eur Cytokine Netw. 2003 Jul-Sep;14(3):158-62.

PMID:14656690

Abstract

To determine the role of CD14 in lipopolysaccharide (LPS)-induced release of chemokines, 16 humans were injected with LPS (4 ng/kg) preceded (-2 h) by intravenous IC14, an anti-human CD14 monoclonal antibody, or placebo. LPS elicited increases in interleukin (IL)-8 concentrations in plasma and in lysates of red blood cell (RBC), polymorphonuclear cell and mononuclear cell fractions, which were all reduced by IC14. LPS also induced rises in the plasma and RBC levels of monocyte chemoattractant protein (MCP)-1, which were diminished by IC14. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, chemokines that in contrast to IL-8 and MCP-1 can not bind to the Duffy antigen receptor for chemokines on RBCs, were only detected in plasma. IC14 attenuated the LPS-induced release of MIP-1beta, but not of MIP-1alpha. IL-8 and MCP-1, but not MIP-1alpha and MIP-1b, circulate in RBC-associated form during endotoxemia. LPS-induced chemokine release is, in part, mediated by an interaction with CD14.

摘要

为确定CD14在脂多糖（LPS）诱导趋化因子释放中的作用，16名受试者在静脉注射LPS（4 ng/kg）前2小时分别注射抗人CD14单克隆抗体IC14或安慰剂。LPS可使血浆、红细胞（RBC）裂解物、多形核细胞和单核细胞组分中的白细胞介素（IL）-8浓度升高，而IC14可降低这些升高水平。LPS还可使血浆和RBC中的单核细胞趋化蛋白（MCP）-1水平升高，IC14可使其降低。巨噬细胞炎性蛋白（MIP）-1α和MIP-1β，与IL-8和MCP-1不同，它们不能与RBC上的趋化因子达菲抗原受体结合，仅在血浆中检测到。IC14可减弱LPS诱导的MIP-1β释放，但不能减弱MIP-1α的释放。在内毒素血症期间，IL-8和MCP-1以与RBC相关的形式循环，而MIP-1α和MIP-1β则不然。LPS诱导的趋化因子释放部分是由与CD14的相互作用介导的。