PMID- 12084877 OWN - NLM STAT- MEDLINE DCOM- 20020723 LR - 20190514 IS - 0028-3878 (Print) IS - 0028-3878 (Linking) VI - 58 IP - 12 DP - 2002 Jun 25 TI - Differential expression of chemokines in inflammatory myopathies. PG - 1779-85 AB - BACKGROUND: Chemokines represent a family of small-molecular-weight cytokines that recruit and activate inflammatory cells in response to inflammation. Invasion of cytotoxic memory T cells and macrophages in nonnecrotic muscle fibers characterizes polymyositis and sporadic inclusion body myositis. Dermatomyositis is a complement-mediated endotheliopathy. Elucidation of the mechanisms guiding lymphocyte diapedesis and trafficking could lead to selective therapeutic interventions. METHODS: Immunoblots and multistep immunofluorescence studies with non-cross-reactive antibodies recognizing interleukin-8, monocyte chemoattractant protein-1 (MCP-1), MCP-3, TARC (thymus and activation regulated cytokine), and RANTES (regulated upon activation, normal T-cell expressed and secreted), using appropriate positive and negative controls. In situ hybridization was used to localize MCP-1 mRNA. RESULTS: MCP-1 protein was strongly expressed on T cells and a subset of macrophages actively invading a proportion of the nonnecrotic muscle fibers in polymyositis and inclusion body myositis alike. Capillaries and arterioles in the vicinity of endomysial inflammatory foci were immunoreactive for MCP-1, with faint or no expression in unaffected parts of the tissue. By contrast, widespread and strong endothelial MCP-1 expression occurred on perifascicular and perimysial endothelia in dermatomyositis, also at sites remote from inflammatory infiltrates. In some control specimens, a subset of capillaries also expressed MCP-1, possibly reflecting a role of this chemokine in normal immune surveillance. MCP-1 mRNA was detected in scattered macrophages in each inflammatory myopathy. All other chemokines were absent. CONCLUSION: Chemokines are differentially expressed in the symptomatic stage of inflammatory myopathies. MCP-1 plays a major role in the myocytotoxicity in polymyositis and inclusion body myositis. MCP-1 may be induced by membranolytic attack complex binding to endothelial cells in dermatomyositis. FAU - De Bleecker, Jan L AU - De Bleecker JL AD - Department of Neurology, University Hospital, Gent, Belgium. jan.debleecker@rug.ac.be FAU - De Paepe, Boel AU - De Paepe B FAU - Vanwalleghem, Iris E AU - Vanwalleghem IE FAU - Schroder, J Michael AU - Schroder JM LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) SB - IM MH - Chemokine CCL2/biosynthesis MH - Chemokines/*biosynthesis MH - Endothelium/immunology/metabolism/pathology MH - Humans MH - Lymph Nodes/immunology/metabolism/pathology MH - Muscle Fibers, Skeletal/immunology/metabolism/pathology MH - Myositis/immunology/*metabolism/*pathology MH - Thymus Gland/immunology/metabolism/pathology MH - Tumor Cells, Cultured EDAT- 2002/06/27 10:00 MHDA- 2002/07/24 10:01 CRDT- 2002/06/27 10:00 PHST- 2002/06/27 10:00 [pubmed] PHST- 2002/07/24 10:01 [medline] PHST- 2002/06/27 10:00 [entrez] AID - 10.1212/wnl.58.12.1779 [doi] PST - ppublish SO - Neurology. 2002 Jun 25;58(12):1779-85. doi: 10.1212/wnl.58.12.1779.