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
C. Bartoli et al., 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, ACT NEUROP, 102(4), 2001, pp. 385-392
The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM
), polymyosititis (PM) and inclusion body myositis (IBM), are a group of au
toimmune diseases characterized by chronic lymphocytic and macrophagic infi
ltration in muscle. The mechanism for recruitment of these cells probably i
nvolves chemokines. We have previously reported that monocyte chemoattracta
nt protein-1 (MCP-1), a beta chemokine, seems to play a major role in monon
uclear cell recruitment especially in DM. Here we have investigated the dis
tribution of the main MCP-1 receptors CCR2A and CCR2B in IIM by polymerase
chain reaction (PCR), immunohistochemistry and in situ hybridization. We ha
ve shown by reverse transcription-PCR that both CCR2A and CCR2B were expres
sed 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 immunohistochem
istry and in situ hybridization we have observed that CCR2 isoforms were ex
pressed by different cell subsets in both normal and IIM muscle. CCR2A was
expressed in vessel walls and by some mononuclear cells, especially in cell
s 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. I
n conclusion, the present study highlights the major role played by MCP-1 a
nd 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 ne
w path towards the understanding of the constitution of mononuclear infiltr
ates in IIM.