PMID- 9574568 OWN - NLM STAT- MEDLINE DCOM- 19980521 LR - 20071114 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 160 IP - 9 DP - 1998 May 1 TI - Monocyte chemoattractant protein-1 synthesis by murine lung fibroblasts modulates CD4+ T cell activation. PG - 4606-14 AB - This study addressed the role of endogenous monocyte chemoattractant protein-1 (MCP-1) in Ag-stimulated lymphokine synthesis and proliferation by CD4+ T cells during their coculture with purified lung fibroblasts or splenic macrophages. Initial experiments showed that fibroblasts exposed to IL-4, TNF alpha, or IL-4 and TNF-alpha (all at 10 ng/ml) for 24 h released five- to eightfold more MCP-1 than similarly treated splenic macrophages. In 72-h coculture experiments, the synthesis of IL-4 by OVA-activated CD4+ T cells added to lung fibroblasts or splenic macrophages was significantly inhibited when endogenous MCP-1 was neutralized using polyclonal anti-MCP-1 antiserum. In these same cocultures, IFN-gamma levels were significantly enhanced. Similarly, IFN-gamma levels were significantly enhanced in 72-h cocultures of a purified peptide derivative-activated CD4+ Th1 clone and lung fibroblasts or splenic macrophages following immunoneutralization of MCP-1. In separate experiments, the selective inhibition of MCP-1 synthesis by lung fibroblasts and splenic macrophages using an MCP-1 antisense oligonucleotide significantly enhanced the proliferation of CD4+ T cells during a 96-h coculture. Taken together, these data suggest that MCP-1 exerts an immunomodulatory effect on CD4+ T cell-derived IL-4 and IFN-gamma release and CD4+ T cell proliferation during cell-to-cell interactions. FAU - Hogaboam, C M AU - Hogaboam CM AD - Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA. FAU - Lukacs, N W AU - Lukacs NW FAU - Chensue, S W AU - Chensue SW FAU - Strieter, R M AU - Strieter RM FAU - Kunkel, S L AU - Kunkel SL LA - eng GR - 1P50HL56402/HL/NHLBI NIH HHS/United States GR - HL31963/HL/NHLBI NIH HHS/United States GR - HL35276/HL/NHLBI NIH HHS/United States GR - etc. PT - Journal Article 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 (Oligonucleotides, Antisense) SB - IM MH - Animals MH - CD4-Positive T-Lymphocytes/*immunology/pathology MH - Cell Division/drug effects MH - Chemokine CCL2/biosynthesis/*immunology MH - Coculture Techniques MH - Female MH - Fibroblasts/immunology/metabolism/pathology MH - Lung/*immunology/pathology MH - *Lymphocyte Activation/drug effects MH - Mice MH - Mice, Inbred CBA MH - Oligonucleotides, Antisense/genetics/pharmacology EDAT- 1998/05/09 00:00 MHDA- 1998/05/09 00:01 CRDT- 1998/05/09 00:00 PHST- 1998/05/09 00:00 [pubmed] PHST- 1998/05/09 00:01 [medline] PHST- 1998/05/09 00:00 [entrez] PST - ppublish SO - J Immunol. 1998 May 1;160(9):4606-14.