Preferential chemotaxis of activated human CD4+ T cells by extracellular cyclophilin

Abstract: The recruitment and trafficking of leu-kocytes are essential aspects of the inflammatory process. Although chemokines are thought to be the main regulators of cell trafficking, extracellu-lar cyclophilins have been shown recently to have potent chemoattracting properties for human leu-kocytes. Cyclophilins are secreted by a variety of cell types and are detected at high levels in tissues with ongoing inflammation. CD147 has been iden-tified as the main signaling receptor for cyclophilin A (CypA) on human leukocytes. It is interesting that the expression of CD147 is elevated on leuko-cytes from inflamed tissue, suggesting a correlation among the presence of extracellular cyclophilins, CD147 expression, and inflammatory responses. Thus, cyclophilin-CD147 interactions may con-tribute directly to the recruitment of leukocytes into inflamed tissues. In the current studies, we show that activated human T lymphocytes express elevated levels of CD147, compared with resting T cells and that these activated T cells migrate more readily to CypA than resting cells. Furthermore, we show that unlike resting CD4 T cells, the cy-clophilin-mediated migration of activated T cells does not require interaction with heparan sulfate receptors but instead, is dependent on CD147 in-teraction alone. Such findings suggest that cyclo-philin-CD147 interactions will be most potent when leukocytes are in an activated state, for ex-ample, during inflammatory responses. Thus, tar-geting cyclophilin-CD147 interactions may pro-vide a novel approach for alleviating tissu