Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation.
Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation.
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DOI：
10.1084/jem.184.5.1939
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发表时间：
1996-11-01
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我们已经克隆了一种新的小鼠CC趋化因子的cDNA从肺在过敏性炎症反应。由该cDNA编码的蛋白质在体外和体内对嗜酸性粒细胞、单核细胞和淋巴细胞具有趋化性。基于其与其他CC趋化因子在序列和功能上的相似性，我们将其命名为小鼠单核细胞趋化蛋白-5（mMCP- 5）。在非炎症条件下，mMCP-5在淋巴结和胸腺中的表达是组成性的，并且通常限于基质细胞。在体内过敏性炎症反应期间，用特异性抗体中和mMCP-5蛋白导致肺中积聚的嗜酸性粒细胞数量减少。此外，体内mMCP- 5 mRNA表达的调节与过敏反应期间肺中其他主要CC趋化因子（包括嗜酸性粒细胞趋化因子）的调节不同。淋巴细胞的存在对于肺中肺泡巨噬细胞和平滑肌细胞表达mMCP-5是必不可少的，并且在过敏性炎症期间，mMCP-5 RNA的诱导早于嗜酸性粒细胞趋化因子Eotaxin的诱导。与嗜酸性粒细胞趋化因子相反，mMCP-5的mRNA可以由肥大细胞产生。根据这些结果，我们推测mMCP-5在过敏性肺部炎症的早期阶段起关键作用。
We have cloned a novel mouse CC chemokine cDNA from the lung during an allergic inflammatory reaction. The protein encoded by this cDNA is chemotactic for eosinophils, monocytes, and lymphocytes in vitro and in vivo. Based on its similarities in sequence and function with other CC chemokines, we have named it mouse monocyte chemotactic protein-5 (mMCP- 5). Under noninflammatory conditions, expression of mMCP-5 in the lymph nodes and thymus is constitutive and is generally restricted to stromal cells. Neutralization of mMCP-5 protein with specific antibodies during an allergic inflammatory reaction in vivo resulted in a reduction in the number of eosinophils that accumulated in the lung. Moreover, mMCP- 5 mRNA expression in vivo is regulated differently from that of other major CC chemokines in the lung during the allergic reaction, including Eotaxin. The presence of lymphocytes is essential for expression of mMCP-5 by alveolar macrophages and smooth muscle cells in the lung, and the induction of mMCP-5 RNA occurs earlier than that of the eosinophil chemokine Eotaxin during allergic inflammation. In contrast to Eotaxin, mRNA for mMCP-5 can be produced by mast cells. From these results, we postulate that mMCP-5 plays a pivotal role during the early stages of allergic lung inflammation.