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Extracellular cyclophilins contribute to the regulation of inflammatory responses.

Abstract
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.
AuthorsKamalpreet Arora, William M Gwinn, Molly A Bower, Alan Watson, Ifeanyi Okwumabua, H Robson MacDonald, Michael I Bukrinsky, Stephanie L Constant
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 1 Pg. 517-22 (Jul 01 2005) ISSN: 0022-1767 [Print] United States
PMID15972687 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, CD
  • Bsg protein, mouse
  • Receptors, Immunologic
  • Basigin
  • Cyclophilin A
  • Cyclophilins
Topics
  • Animals
  • Antigens, CD (metabolism)
  • Basigin
  • Chemotaxis, Leukocyte
  • Cyclophilin A (metabolism)
  • Cyclophilins (metabolism)
  • Extracellular Space (enzymology, immunology)
  • Female
  • In Vitro Techniques
  • Inflammation (enzymology, etiology, immunology, pathology)
  • Lung (immunology, pathology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils (immunology, pathology)
  • Receptors, Immunologic (metabolism)
  • Signal Transduction

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