CCR2A and CCR2B, the two isoforms of the monocyte chemoattractant protein-1 receptor are up-regulated and expressed by different cell subsets in idiopathic inflammatory myopathies.
The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyosititis (PM) and inclusion body myositis (IBM), are a group of autoimmune diseases characterized by chronic lymphocytic and macrophagic infiltration in muscle. The mechanism for recruitment of these cells probably involves chemokines. We have previously reported that monocyte chemoattractant protein-1 (MCP-1), a beta chemokine, seems to play a major role in mononuclear cell recruitment especially in DM. Here we have investigated the distribution of the main MCP-1 receptors CCR2A and CCR2B in IIM by polymerase chain reaction (PCR), immunohistochemistry and in situ hybridization. We have shown by reverse transcription-PCR that both CCR2A and CCR2B were expressed at low level in normal muscle and that CCR2A was up-regulated in IIM (P=0.02) and was higher in PM and IBM than in DM (P=0.04). By immunohistochemistry and in situ hybridization we have observed that CCR2 isoforms were expressed by different cell subsets in both normal and IIM muscle. CCR2A was expressed in vessel walls and by some mononuclear cells, especially in cells involved in partial invasion in PM and IBM. CCR2B expression was observed in all satellite cells, in the muscular domain of neuromuscular junctions and in some regenerative fibers of IIM, but not in inflammatory exudates. In conclusion, the present study highlights the major role played by MCP-1 and its counter-receptor CCR2 in the pathophysiology of IIM, and shows that the CCR2 receptors are cell specific. The variation of the total amount of CCR2A and its local distribution according to the type of IIM might be a new path towards the understanding of the constitution of mononuclear infiltrates in IIM.
Bartoli
C
C
Laboratoire de Biopathologie Nerveuse et Musculaire, Faculté de médecine, IBDM Marseille, France.
Civatte
M
M
Pellissier
J F
JF
Figarella-Branger
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology
C515334:CCR2 protein, human; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine