Vol. 186, No. 2, 1992

BIOCHEMICAL

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

July 31, 1992

Pages

LEUKOCYTE

CHEMOTACTIC

ACTIVITY

1178-1183

OF FKBP AND INHIBITION

BY

FK506 Maria C. Leiva and C. Richard Lyttle* Departmentof Obstetricsand Gynecology, Division of Reproductive Biology, University of Pennsylvania,Philadelphia,PA 19104

Received

June

12,

1992

Cyclophilin, the cyclosporin A binding protein and memberof the immunophilinfamily of proteins, demonstratesleukocyte chemotacticactivity. In this study we demonstratethat FKBP, the FK.506 and rapamycin binding protein, alsodisplaysleukocyte chemotacticactivity. The chemotactic activity of FKBP is inhibited by FK506, however, IX506 was unableto inhibit cyclophilin-stimulatedchemotacticactivity. Rapamycinwasunableto prevent the chemotactic activity of FKBP, similarly, the CsA analogueMe6Ala-CsA while displaying cyclophilin binding was unableto block cyclophilin-stimulatedchemotacticactivity. Theseresultssuggestthat in addition to their intracellular role the immunophilinsmay alsofunction aschemotacticagents, furthermore this activity is modulatedby immunosuppressants. 0 1992Academic Press,I”