Processing by CD26/dipeptidyl-peptidase IV reduces the chemotactic and anti-HIV-1 activity of stromal-cell-derived factor-1alpha

FEBS Lett. 1998 Jul 31;432(1-2):73-6. doi: 10.1016/s0014-5793(98)00830-8.

Abstract

The chemokine stromal-cell-derived factor-1alpha (SDF-1alpha) chemoattracts lymphocytes and CD34+ haematopoietic progenitors and is the ligand for CXCR4 (CXC chemokine receptor 4), the main co-receptor for T-tropic HIV-1 strains. SDF-1alpha was NH2-terminally cleaved to SDF-1alpha(3-68) by dipeptidyl-peptidase IV (CD26/DPP IV), which is present in blood in soluble and membrane-bound form. SDF-1alpha(3-68) lost both lymphocyte chemotactic and CXCR4-signaling properties. However, SDF-1alpha(3-68) still desensitized the SDF-1alpha(1-68)-induced Ca2+ response. In contrast to CD26/DPP IV-processed RANTES(3-68), SDF-1alpha(3-68) had diminished potency to inhibit HIV-1 infection. Thus, CD26/DPP IV impairs the inflammatory and haematopoietic potency of chemokines but plays a dual role in AIDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / metabolism
  • Anti-HIV Agents / pharmacology*
  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CXC / metabolism
  • Chemokines, CXC / pharmacology*
  • Chemotaxis, Leukocyte
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dose-Response Relationship, Drug
  • HIV-1 / drug effects
  • Humans
  • Lymphocytes
  • Peptide Fragments / pharmacology*
  • Protein Processing, Post-Translational*
  • Receptors, CXCR4 / metabolism
  • Signal Transduction

Substances

  • Anti-HIV Agents
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CXC
  • Peptide Fragments
  • Receptors, CXCR4
  • Dipeptidyl Peptidase 4