Inhibition of murine neutrophil recruitment in vivo by CXC chemokine receptor antagonists.
Inhibition of murine neutrophil recruitment in vivo by CXC chemokine receptor antagonists.
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DOI：
10.4049/jimmunol.163.5.2829
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发表时间：
1999-09
影响因子：
4.4
通讯作者：
S. McColl;I. Clark‐Lewis
中科院分区：
文献类型：
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作者：
S. McColl;I. Clark‐Lewis
在这项研究中，我们研究了趋化因子受体拮抗剂在小鼠中预防中性粒细胞外渗的能力。两种小鼠CXC趋化因子，巨噬细胞炎症蛋白(MIP)-2和KC，刺激白细胞积聚到s.c.气袋中，尽管MIP-2更有效。白细胞浸润在本质上几乎完全是中性粒细胞。一种人类CXC趋化因子拮抗剂生长相关癌基因(GRO)- α(8-73)可以抑制MIP-2诱导的钙动员，但对骨髓分离的白细胞中的血小板活化因子没有作用，这表明这种拮抗剂可以抑制MIP-2对小鼠白细胞的活性。用GROalpha（8-73）预处理小鼠，以剂量依赖的方式抑制mip -2诱导的中性粒细胞内流，其水平与对照组无显著差异。此外，该拮抗剂还能有效抑制tnf - α、LPS和il -1 β诱导的白细胞募集。先前用GROalpha（8-73）或血小板因子4类似物PF4（9-70）治疗小鼠，也能抑制MIP-2对腹腔的白细胞浸润。本研究结果表明：1)MIP-2和KC的小鼠受体muCXCR2在促炎剂作用下向sc组织和腹腔募集中性粒细胞中起主要作用；2)CXCR2受体拮抗剂在体内可预防急性炎症。
In this study, we have examined the ability of chemokine receptor antagonists to prevent neutrophil extravasation in the mouse. Two murine CXC chemokines, macrophage-inflammatory protein (MIP)-2 and KC, stimulated the accumulation of leukocytes into s.c. air pouches, although MIP-2 was considerably more potent. The leukocyte infiltrate was almost exclusively neutrophilic in nature. A human CXC chemokine antagonist, growth-related oncogene (GRO)-alpha(8-73), inhibited calcium mobilization induced by MIP-2, but not by platelet-activating factor in leukocytes isolated from the bone marrow, indicating that this antagonist inhibits MIP-2 activity toward murine leukocytes. Pretreatment of mice with GROalpha(8-73) inhibited, in a dose-dependent manner, the MIP-2-induced influx of neutrophils to levels that were not significantly different from control values. Moreover, this antagonist was also effective in inhibiting the leukocyte recruitment induced by TNF-alpha, LPS, and IL-1beta. Leukocyte infiltration into the peritoneal cavity in response to MIP-2 was also inhibited by prior treatment of mice with GROalpha(8-73) or the analogue of platelet factor 4, PF4(9-70). The results of this study indicate 1) that the murine receptor for MIP-2 and KC, muCXCR2, plays a major role in neutrophil recruitment to s.c. tissue and the peritoneal cavity in response to proinflammatory agents and 2) that CXCR2 receptor antagonists prevent acute inflammation in vivo.