Localization of the alpha-chemokine SDF-1 and its receptor CXCR4 in idiopathic inflammatory myopathies.
We studied the distribution of stromal cell-derived factor 1 isoforms alpha and beta, and their receptor CXCR4, in polymyositis, sporadic inclusion body myositis and dermatomyositis using in situ hybridization, immunohistochemistry, immunofluorescence and Western blotting. In control muscle, polymyositis and sporadic inclusion body myositis, stromal cell-derived factor-1alpha expression was noted in muscle fibers, while stromal cell-derived factor-1beta and CXCR4 were predominantly localized to capillaries and arterioles. In dermatomyositis, stromal cell-derived factor-1beta immunoreactivity of blood vessels was focally increased. The vast majority of inflammatory cells in idiopathic inflammatory myopathies were CXCR4 positive. A subset of helper T-cells and macrophages expressed stromal cell-derived factor-1alpha, while only rare inflammatory cells expressed stromal cell-derived factor-1beta. A significant increase of stromal cell-derived factor-1alpha and CXCR4 was observed in protein extracts of idiopathic inflammatory myopathies in comparison with normal controls. The abundance of both CXCR4 and its ligand stromal cell-derived factor-1 implicates their interaction in the pathogenesis of idiopathic inflammatory myopathies and identifies these proteins as possible targets for selective immune therapy.
De Paepe
Boel
B
Department of Neurology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
Schröder
J Michael
JM
Martin
Jean-Jacques
JJ
Racz
Gabor Z
GZ
De Bleecker
Jan L
JL
D015703:Antigens, CD / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D003882:Dermatomyositis / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009220:Myositis / Q000235:genetics / Q000378:metabolism*; D018979:Myositis, Inclusion Body / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D015703:Antigens, CD; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D020033:Protein Isoforms; D019718:Receptors, CXCR4