Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats.
Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats.
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DOI：
10.4049/jimmunol.156.5.1963
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发表时间：
1996-03
影响因子：
4.4
通讯作者：
Hagen Schmal;T. Shanley;M. Jones;H. Friedl;P. Ward
中科院分区：
文献类型：
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作者：
Hagen Schmal;T. Shanley;M. Jones;H. Friedl;P. Ward
巨噬细胞炎性蛋白-2（MIP-2）是一种C-X-C趋化因子，对中性粒细胞具有趋化活性。大鼠MIP-2被克隆并表达为7.9 kDa肽，其在10至250 nM的浓度下表现出剂量依赖性中性粒细胞趋化活性。兔多克隆抗体的7.9-kDa的肽显示反应性的蛋白质印迹分析，并抑制其在体外趋化活性。交叉脱敏趋化实验表明，MIP-2和相关的趋化因子，姜黄素诱导的中性粒细胞趋化因子引起的趋化反应，可能是通过一个共同的受体介导的。此外，通过将人中性粒细胞暴露于GRO-α或大鼠MIP-2来阻断对人GRO-α的趋化反应，表明该受体介导的反应是保守的。LPS注入大鼠肺后，MIP-2 mRNA表达呈时间依赖性上调，6 h达高峰。在这些动物的支气管肺泡灌洗液中检测到MIP-2蛋白，这些液体中存在的大量趋化活性归因于MIP-2。在肺内滴注MIP-2抗体的基础上，发现气道滴注LPS后肺内中性粒细胞积聚是MIP-2依赖性的。这些数据表明，MIP-2在LPS诱导的大鼠肺部炎症反应中起着重要作用，并且是中性粒细胞完全募集所必需的。
Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to the 7.9-kDa peptide showed reactivity by western blot analysis and suppressed its in vitro chemotactic activity. Cross-desensitization chemotaxis experiments suggested that the chemotactic responses elicited by MIP-2 and the related chemokine, cytokine-induced neutrophil chemoattractant, may be mediated through a common receptor. Also, chemotactic responses to human GRO-alpha were blocked by exposure of human neutrophils to either GRO-alpha or rat MIP-2, suggesting conservation of this receptor-mediated response. After LPS instillation into rat lung, mRNA for MIP-2 was up-regulated in a time-dependent manner, peaking at 6 h. MIP-2 protein was detected in bronchoalveolar lavage fluids of these animals and a significant amount of chemotactic activity present in these fluids was attributed to MIP-2. On the basis of intrapulmonary instillation of Ab to MIP-2, neutrophil accumulation in lungs after airway instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils.