PMID- 8977213 OWN - NLM STAT- MEDLINE DCOM- 19970130 LR - 20071114 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 158 IP - 1 DP - 1997 Jan 1 TI - Monocyte chemoattractant protein-1 is sufficient for the chemotaxis of monocytes and lymphocytes in transgenic mice but requires an additional stimulus for inflammatory activation. PG - 376-83 AB - 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. FAU - Gunn, M D AU - Gunn MD AD - Daiichi Research Center, Cardiovascular Research Institute, University of California at San Francisco 94143, USA. FAU - Nelken, N A AU - Nelken NA FAU - Liao, X AU - Liao X FAU - Williams, L T AU - Williams LT LA - eng GR - K11 HL02388/HL/NHLBI NIH HHS/United States GR - P01 HL43821/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokine CCL2) RN - 0 (Glucans) RN - 0 (Lipopolysaccharides) SB - IM MH - Animals MH - Chemokine CCL2/*pharmacology MH - Chemotaxis, Leukocyte/*drug effects MH - Drug Synergism MH - Epithelium/metabolism MH - Glucans/pharmacology MH - Humans MH - Inflammation/*immunology MH - Lipopolysaccharides/pharmacology MH - Lymphocyte Activation/*drug effects MH - Lymphocytes/*drug effects MH - Macrophage Activation/*drug effects MH - Mice MH - Mice, Transgenic MH - Monocytes/*drug effects MH - Pulmonary Alveoli/metabolism EDAT- 1997/01/01 00:00 MHDA- 1997/01/01 00:01 CRDT- 1997/01/01 00:00 PHST- 1997/01/01 00:00 [pubmed] PHST- 1997/01/01 00:01 [medline] PHST- 1997/01/01 00:00 [entrez] PST - ppublish SO - J Immunol. 1997 Jan 1;158(1):376-83.