Adenosine A2A receptor blockade or deletion diminishes fibrocyte accumulation in the skin in a murine model of scleroderma, bleomycin-induced fibrosis.
Peripheral blood fibrocytes are a newly identified circulating leukocyte subpopulation that migrates into injured tissue where it may display fibroblast-like properties and participate in wound healing and fibrosis of skin and other organs. Previous studies in our lab demonstrated that A(2A) receptor-deficient and A(2A) antagonist-treated mice were protected from developing bleomycin-induced dermal fibrosis, thus the aim of this study was to determine whether the adenosine A(2A) receptor regulates recruitment of fibrocytes to the dermis in this bleomycin-induced model of dermal fibrosis. Sections of skin from normal mice and bleomycin-treated wild type, A(2A) knockout and A(2A) antagonist-treated mice were stained for Procollagen alpha2 Type I and CD34 and the double stained cells, fibrocytes, were counted in the tissue sections. There were more fibrocytes in the dermis of bleomycin-treated mice than normal mice and the increase was abrogated by deletion or blockade of adenosine A(2A) receptors. Because fibrocytes play a central role in tissue fibrosis these results suggest that diminished adenosine A(2A) receptor-mediated recruitment of fibrocytes into tissue may play a role in the pathogenesis of fibrosing diseases of the skin. Moreover, these results provide further evidence that adenosine A(2A) receptors may represent a new target for the treatment of such fibrosing diseases as scleroderma or nephrogenic fibrosing dermopathy.
Katebi
Majid
M
Division of Clinical Pharmacology, Department of Medicine, New York University School of Medicine, 550 First Ave., New York, NY 10016, USA.
Fernandez
Patricia
P
Chan
Edwin S L
ES
Cronstein
Bruce N
BN
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018952:Antigens, CD34 / Q000096:biosynthesis; D001761:Bleomycin / Q000494:pharmacology*; D003094:Collagen / Q000737:chemistry; D003238:Connective Tissue / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis / Q000209:etiology* / Q000378:metabolism; D017353:Gene Deletion; D051379:Mice; D008954:Models, Biological; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D058917:Adenosine A2 Receptor Antagonists; D000903:Antibiotics, Antineoplastic; D018952:Antigens, CD34; D043705:Receptor, Adenosine A2A; D001761:Bleomycin; D003094:Collagen