Leukocyte chemotactic activity of FKBP and inhibition by FK506.
Cyclophilin, the cyclosporin A binding protein and member of the immunophilin family of proteins, demonstrates leukocyte chemotactic activity. In this study we demonstrate that FKBP, the FK506 and rapamycin binding protein, also displays leukocyte chemotactic activity. The chemotactic activity of FKBP is inhibited by FK506, however, FK506 was unable to inhibit cyclophilin-stimulated chemotactic activity. Rapamycin was unable to prevent the chemotactic activity of FKBP, similarly, the CsA analogue Me6Ala-CsA while displaying cyclophilin binding was unable to block cyclophilin-stimulated chemotactic activity. These results suggest that in addition to their intracellular role the immunophilins may also function as chemotactic agents, furthermore this activity is modulated by immunosuppressants.
Leiva
M C
MC
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia 19104.
Lyttle
C R
CR
D000591:Amino Acid Isomerases / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D003524:Cyclosporins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D019696:Peptidylprolyl Isomerase; D011090:Polyenes / Q000494:pharmacology; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D011090:Polyenes; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus; D016559:Tacrolimus