| Literature DB >> 23964991 |
Miroslav Malesevic1, Danny Gutknecht, Erik Prell, Claudia Klein, Michael Schumann, Romana A Nowak, Jan C Simon, Cordelia Schiene-Fischer, Anja Saalbach.
Abstract
Leukocyte trafficking and recruitment is a critical process in host immune surveillance and in inflammatory diseases. Extracellular cyclophilins (eCyps) have been identified as a novel class of chemotactic mediators. The impact of eCyp/CD147 interactions for the recruitment of leukocytes during inflammation was analyzed using a structurally simplified cell-impermeable eCyp inhibitor. This compound was highly effective at inhibiting leukocyte migration toward CypA in vitro as well as in the recruitment of leukocytes during inflammation in a mouse model of experimentally induced peritonitis and delayed-type hypersensitivity reaction. By using CD147-/- mice in combination with the cell-impermeable eCyp inhibitor, we were able to show that the action of eCyps in inflammation is exclusively mediated by interaction with CD147. Our findings suggest that blocking eCyps may be an effective therapeutic target for reducing inflammatory diseases associated with leukocyte recruitment.Entities:
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Year: 2013 PMID： 23964991 DOI： 10.1021/jm4007577
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446