Increased expression of beta-chemokines in muscle of patients with inflammatory myopathies.
Idiopathic inflammatory myopathies (IIM) are muscle diseases of autoimmune pathogenesis characterized by mononuclear cell infiltration within muscle tissue. Since immune cell homing and accumulation at the site of antigenic challenge is usually mediated by chemokines, we evaluated the expression of 2 beta-chemokines--monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha)--by immunohistochemistry and polymerase chain reaction in muscles of polymyositis, inclusion body myositis, and dermatomyositis patients, and related their expression to immunopathological alterations in muscle. MCP-1 and MIP-1alpha transcripts were detected by PCR in all IIM muscles, but not in controls. By immunohistochemistry, the chemokines were found in all IIM muscle sections located in infiltrating inflammatory cells and also in neighboring extracellular matrix. The extent to which extracellular matrix was filled by each chemokine differed in each disease. In view of the known ability of chemokines to bind extracellular matrix and their possible synthesis by extracellular matrix components, we suggest that chemokine storage in the extracellular matrix can act as a microenvironmental factor amplifying lymphocyte activation and migration, thereby maintaining the autoimmune attack against unknown muscle antigens.
Confalonieri
P
P
Divisione Malattie Neuromuscolari, Istituto Nazionale Neurologico Carlo Besta, Milan, Italy.
Bernasconi
P
P
Megna
P
P
Galbiati
S
S
Cornelio
F
F
Mantegazza
R
R
D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000032:analysis* / Q000235:genetics; D003882:Dermatomyositis / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000235:genetics; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D009220:Myositis / Q000235:genetics / Q000378:metabolism*; D018979:Myositis, Inclusion Body / Q000235:genetics / Q000378:metabolism; D017285:Polymyositis / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D012313:RNA