CD26/dipeptidyl-peptidase IV down-regulates the eosinophil chemotactic potency, but not the anti-HIV activity of human eotaxin by affecting its interaction with CC chemokine receptor 3

Chemokines attract and activate distinct sets of leukocytes. The CC chemoki ne eotaxin has been characterized as an important mediator in allergic reac tions because it selectively attracts eosinophils, Th-2 lymphocytes, and ba sophils, Human eotaxin has a penultimate proline, indicating that it might be a substrate for dipeptidyl-peptidase TV (CD26/DPP IV). In this study we demonstrate that eotaxin is efficiently cleaved by CD26/DPP IV and that the NH2-terminal truncation affects its biological activity. CD26/DPP IV-trunc ated eotaxin(3-74) showed reduced chemotactic activity for eosinophils and impaired binding and signaling properties through the CC chemokine receptor 3, Moreover, eotaxin(3-74) desensitized calcium signaling and inhibited ch emotaxis toward intact eotaxin. In addition, HIV-2 infection of CC chemokin e receptor 3-transfected cells was inhibited to a similar extent by eotaxin and eotaxin(3-74). Thus, CD26/DPP TV differently regulates the chemotactic and antiviral potencies of eotaxin by the removal of two NH2-terminal resi dues. This physiological processing may be an important down-regulatory mec hanism, limiting eotaxin-mediated inflammatory responses.