Endogenous monocyte chemoattractant protein-1 (MCP-1) protects mice in a model of acute septic peritonitis: cross-talk between MCP-1 and leukotriene B4.
Endogenous monocyte chemoattractant protein-1 (MCP-1) protects mice in a model of acute septic peritonitis: cross-talk between MCP-1 and leukotriene B4.
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DOI：
10.4049/jimmunol.163.11.6148
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发表时间：
1999-12
影响因子：
4.4
通讯作者：
Akihiro Matsukawa;C. Hogaboam;N. Lukacs;Pamela M. Lincoln;R. Strieter;S. L. Kunkel
中科院分区：
文献类型：
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作者：
Akihiro Matsukawa;C. Hogaboam;N. Lukacs;Pamela M. Lincoln;R. Strieter;S. L. Kunkel
我们研究了单核细胞趋化蛋白（MCP）-1在盲肠结扎穿孔（CLP）诱导的小鼠脓毒性腹膜炎模型中的作用。最初的研究表明，CLP诱导腹膜中MCP-1产生的急剧增加，随后增加白细胞的募集。用抗MCP-1抗血清阻断MCP-1可显著降低CLP后的存活率，并伴有腹膜活菌的恢复增强。这可能是由于巨噬细胞和中性粒细胞的募集和活化减少所致。为了了解MCP-1可能影响中性粒细胞浸润的机制，监测了已知吸引中性粒细胞的趋化因子的水平，这表明巨噬细胞炎性蛋白（MIP）-2，KC和MIP-1 α的腹膜水平没有被抗MCP-1抗体改变。然而，抗MCP-1抗体使腹膜白三烯B4（LTB 4）水平降低了59%。将MCP-1腹腔注射到正常小鼠中导致腹膜中LTB 4水平升高。在体外，MCP-1刺激产生LTB 4从腹腔巨噬细胞，在剂量依赖性的方式。特异性LTB 4受体拮抗剂（CP-105，696）抑制CLP诱导的中性粒细胞和巨噬细胞的募集，伴随着腹膜中MCP-1水平的降低。最后，CP-105，696给药对CLP后小鼠的存活极为不利。这些实验表明，内源性MCP-1作为一种间接介质，通过产生LTB 4吸引中性粒细胞，并表明在脓毒性腹膜炎期间MCP-1和脂质介质LTB 4之间可能发生串扰。
We investigated the involvement of monocyte chemoattractant protein (MCP)-1 in a murine model of septic peritonitis induced by cecal ligation and puncture (CLP). Initial studies demonstrated that CLP induced a dramatic increase in MCP-1 production in the peritoneum, followed by an increase in the recruitment of leukocytes. MCP-1 blockade with anti-MCP-1 antiserum significantly decreased the survival rate following CLP, which was accompanied by an enhanced recovery of viable bacteria from the peritoneum. This was likely due to the reduction in the recruitment and activation of both macrophages and neutrophils. To understand the mechanisms whereby MCP-1 may influence neutrophil infiltration, levels of chemokines known to attract neutrophils were monitored, which showed that peritoneal levels of macrophage-inflammatory protein (MIP)-2, KC, and MIP-1alpha were not altered with anti-MCP-1 Abs. However, anti-MCP-1 Abs reduced the peritoneal levels of leukotriene B4 (LTB4) by 59%. The i.p. injection of MCP-1 into normal mice resulted in elevated levels of LTB4 in the peritoneum. In vitro, MCP-1 stimulated the production of LTB4 from peritoneal macrophages, in a dose-dependent manner. A specific LTB4 receptor antagonist (CP-105, 696) inhibited CLP-induced recruitment of both neutrophils and macrophages, which was accompanied by a reduced level of MCP-1 in the peritoneum. Finally, administration of CP-105,696 was extremely detrimental to the survival of mice following CLP. These experiments demonstrate that endogenous MCP-1 serves as an indirect mediator to attract neutrophils via the production of LTB4, and suggest the cross-talk can occur between MCP-1 and the lipid mediator LTB4 during septic peritonitis.