PROCESSING BY CD26 DIPEPTIDYL-PEPTIDASE-IV REDUCES THE CHEMOTACTIC AND ANTI-HIV-1 ACTIVITY OF STROMAL-CELL-DERIVED FACTOR-1-ALPHA/

The chemokine stromal-cell-derived factor-let (SDF-1 alpha) chemoattra cts lymphocytes and CD34(+) haematopoietic progenitors and is the liga nd for CXCR4 (CXC chemokine receptor 4), the main co-receptor for T-tr opic HIV-1 strains. SDF-1 alpha was NH2-terminally cleaved to SDF-1 al pha?(3-68) by dipeptidyl-peptidase IV (CD26/DPP IV), which is present in blood in soluble and membrane-bound form. SDF-1 alpha(3-68) lost bo th lymphocyte chemotactic and CXCR4-signaling properties. However, SDF -1 alpha(3-68) still desensitized the SDF-1 alpha(1-68)-induced Ca2+ r esponse. In contrast to CD26/DPP IV-processed RANTES(3-68), SDF-1 alph a(3-68) had diminished potency to inhibit HIV-I infection. Thus, CD26/ DPP IV impairs the inflammatory and haematopoietic potency of chemokin es but plays a dual role in AIDS. (C) 1998 Federation of European Bioc hemical Societies.