| 摘要 |
The interferon (IFN)-inducible chemokines, i.e. IFN- gamma inducible protein-10 (IP-10), monokine induced by IFN- gamma (Mig) and IFN-inducible T-cell alpha -chemoattractant (I-TAC), share a unique CXC chemokine receptor (CXCR3). Recently, a highly specific membrane-bound protease and lymphocyte surface marker CD26/dipeptidyl peptidase IV (DPP IV) was found to be responsible for posttranslational processing of chemokines. Removal of NH2-terminal dipeptides by CD26/DPP IV alters chemokine receptor binding and signaling, and hence inflammatory and anti-HIV activities. CD26/DPP IV and CXCR3 are both markers for Th1 lymphocytes and, moreover, CD26/DPP IV is present in a soluble, active form in human plasma. Here we report that I-TAC was efficiently cleaved by CD26/DPP IV, whereas for Mig the kinetics were 10-fold slower. Processing of IP-10 and I-TAC by CD26/DPP IV resulted in reduced CXCR3 binding properties, loss of calcium signaling capacity through CXCR3 and more than 10-fold reduced chemotactic potency. Moreover, CD26/DPP IV-cleaved IP-10 acted as a chemotaxis antagonist. In contrast, CD26//DPP IV-truncated IP-10 retained its ability to inhibit the angiogenic activity of interleukin-8 in the rabbit cornea micropocket model. Our data demonstrate a negative feedback regulation by CD26/DPP IV in CXCR3-mediated inflammation without affecting the angiostatic potential of the CXCR3 ligand IP-10.
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