Extracellular cyclophilins contribute to the regulation of inflammatory responses.
The main regulators of leukocyte trafficking during inflammatory responses are chemokines. However, another class of recently identified chemotactic agents is extracellular cyclophilins, the proteins mostly known as receptors for the immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte chemotaxis in vitro and have been detected at elevated levels in inflamed tissues, suggesting that they might contribute to inflammatory responses. We recently identified CD147 as the main signaling receptor for cyclophilin A. In the current study we examined the contribution of cyclophilin-CD147 interactions to inflammatory responses in vivo using a mouse model of acute lung injury. Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab) or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These findings are the first to demonstrate the significant contribution of cyclophilins to inflammatory responses and provide a potentially novel approach for reducing inflammation-mediated diseases.
Arora
Kamalpreet
K
Department of Microbiology and Tropical Medicine, George Washington University, Washington, D.C. 20037, USA.
Gwinn
William M
WM
Bower
Molly A
MA
Watson
Alan
A
Okwumabua
Ifeanyi
I
MacDonald
H Robson
HR
Bukrinsky
Michael I
MI
Constant
Stephanie L
SL
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051926:Basigin; D002634:Chemotaxis, Leukocyte; D021984:Cyclophilin A / Q000378:metabolism; D021983:Cyclophilins / Q000378:metabolism*; D005110:Extracellular Space / Q000201:enzymology / Q000276:immunology; D005260:Female; D066298:In Vitro Techniques; D007249:Inflammation / Q000201:enzymology / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction
D015703:Antigens, CD; C497887:Bsg protein, mouse; D011971:Receptors, Immunologic; D051926:Basigin; D021984:Cyclophilin A; D021983:Cyclophilins