PMID- 8160772 OWN - NLM STAT- MEDLINE DCOM- 19940516 LR - 20220331 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 144 IP - 4 DP - 1994 Apr TI - Production of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 alpha by inflammatory granuloma fibroblasts. PG - 711-8 AB - The formation of hepatic granulomas around persistently deposited Schistosoma mansoni eggs leads to parenchymal damage, ongoing fibrosis, and ultimate loss of liver function. In this study, the production of macrophage inflammatory protein-1 alpha (MIP-1) and monocyte chemoattractant protein-1 (MCP-1) by granuloma fibroblasts was examined to establish the potential contribution of intragranuloma fibroblasts to the maintenance of the chronic inflammation. Isolated fibroblasts from dispersed acute infection hepatic granulomas were grown in tissue culture for 3 to 4 weeks and used on the third or fourth passage. We initially surveyed fibroblasts for production of MIP-1 and MCP-1 by reverse transcription-polymerase chain reaction (RT-PCR) after stimulation with interleukin (IL)-1, tumor necrosis factor, interferon (IFN)-gamma, IL-4, or IL-10: cytokines found within the granuloma. These studies demonstrated constitutive expression of MCP-1 and differential up-regulation of MIP-1 on cytokine stimulation. Protein expression was then verified by immunohistochemical localization of MIP-1 and MCP-1 in paraformaldehyde-fixed fibroblasts and by direct quantitation of MIP-1 and MCP-1 in culture supernatants by specific ELISAs. These studies demonstrated constitutive expression of MCP-1 in unstimulated and cytokine-stimulated granuloma fibroblasts. In contrast, IL-1 (0.1 to 2.5 ng/ml), IFN-gamma (10 micrograms/ml), and IL-10 (2.5 to 10 ng/ml) were able to induce the significant production of MIP-1 by the granuloma fibroblasts. Interestingly, normal noninflammatory fibroblasts from uninfected mice showed no significant production of MIP-1 or MCP-1 in response to these cytokines. These results suggest that granuloma fibroblasts may be phenotypically altered compared with normal fibroblasts and have a significant role in leukocyte recruitment, granuloma growth, and maintenance of the egg-induced lesion. FAU - Lukacs, N W AU - Lukacs NW AD - Department of Pathology, University of Michigan Medical School, Ann Arbor. FAU - Chensue, S W AU - Chensue SW FAU - Smith, R E AU - Smith RE FAU - Strieter, R M AU - Strieter RM FAU - Warmington, K AU - Warmington K FAU - Wilke, C AU - Wilke C FAU - Kunkel, S L AU - Kunkel SL LA - eng GR - HL-02401/HL/NHLBI NIH HHS/United States GR - HL-35276/HL/NHLBI NIH HHS/United States GR - HL-3693/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL4) RN - 0 (Chemotactic Factors) RN - 0 (Cytokines) RN - 0 (DNA Primers) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (Monokines) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Base Sequence MH - Cells, Cultured MH - Chemokine CCL2 MH - Chemokine CCL4 MH - Chemotactic Factors/*biosynthesis/genetics MH - Cytokines/*biosynthesis/genetics MH - DNA Primers MH - Female MH - Fibroblasts/*immunology MH - Gene Expression MH - Granuloma/*immunology/pathology MH - Immunoenzyme Techniques MH - Liver Diseases, Parasitic/immunology/pathology MH - Macrophage Inflammatory Proteins MH - Mice MH - Mice, Inbred CBA MH - Molecular Sequence Data MH - Monokines/*biosynthesis/genetics MH - Polymerase Chain Reaction MH - RNA, Messenger/analysis MH - Schistosomiasis mansoni/immunology/pathology PMC - PMC1887251 EDAT- 1994/04/01 00:00 MHDA- 1994/04/01 00:01 PMCR- 1994/10/01 CRDT- 1994/04/01 00:00 PHST- 1994/04/01 00:00 [pubmed] PHST- 1994/04/01 00:01 [medline] PHST- 1994/04/01 00:00 [entrez] PHST- 1994/10/01 00:00 [pmc-release] PST - ppublish SO - Am J Pathol. 1994 Apr;144(4):711-8.