Gunn M D, Nelken N A, Liao X, Williams L T
Daiichi Research Center, Cardiovascular Research Institute, University of California at San Francisco 94143, USA.
J Immunol. 1997 Jan 1;158(1):376-83.
Monocyte chemoattractant protein-1 (MCP-1), a chemotactic cytokine, acts in vitro as a chemotactic and activating factor for multiple types of leukocytes. To determine the chemotactic and activating effects of MCP-1 in vivo, we constructed transgenic mice that express human MCP-1 in type II alveolar epithelial cells and secrete it into the bronchoalveolar space. We found that MCP-1 overexpression led to a marked increase in the numbers of both monocytes and lymphocytes that could be recovered by bronchoalveolar lavage. This accumulation of mononuclear leukocytes could be reversed by the administration of an MCP-1-blocking Ab. In spite of its chemotactic effect, MCP-1 expression did not cause the inflammatory activation of accumulated leukocytes. Lungs of MCP-1 transgenic mice also showed no morphologic evidence of inflammation. However, MCP-1 mice had an increased sensitivity to other inflammatory stimuli. MCP-1 mice treated with either i.p. LPS or i.v. yeast wall glucan developed consolidated pulmonary infiltrates consisting predominantly of macrophages. Nontransgenic mice developed no such infiltrates. These results demonstrate that MCP-1 is chemotactic for monocytes and lymphocytes in vivo and that MCP-1 expression alone does not cause inflammatory activation of cells, but leads to an enhanced inflammatory response upon treatment with other stimuli.
单核细胞趋化蛋白-1（MCP-1）是一种趋化性细胞因子，在体外作为多种白细胞的趋化和激活因子发挥作用。为了确定MCP-1在体内的趋化和激活作用，我们构建了在II型肺泡上皮细胞中表达人MCP-1并将其分泌到支气管肺泡腔的转基因小鼠。我们发现，MCP-1的过表达导致支气管肺泡灌洗可回收的单核细胞和淋巴细胞数量显著增加。这种单核白细胞的聚集可通过给予MCP-1阻断抗体而逆转。尽管MCP-1有趋化作用，但其表达并未引起聚集白细胞的炎症激活。MCP-1转基因小鼠的肺也未显示出炎症的形态学证据。然而，MCP-1小鼠对其他炎症刺激的敏感性增加。用腹腔注射脂多糖（LPS）或静脉注射酵母细胞壁葡聚糖处理的MCP-1小鼠出现主要由巨噬细胞组成的肺实变浸润。非转基因小鼠未出现此类浸润。这些结果表明，MCP-1在体内对单核细胞和淋巴细胞具有趋化作用，单独的MCP-1表达不会引起细胞的炎症激活，但在用其他刺激物处理后会导致炎症反应增强。
