Processing by CD26/dipeptidyl-peptidase IV reduces the chemotactic and anti-HIV-1 activity of stromal-cell-derived factor-1alpha.
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.
Proost
P
P
Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Belgium. Paul.Proost@rega.kuleuven.ac.be
Struyf
S
S
Schols
D
D
Durinx
C
C
Wuyts
A
A
Lenaerts
J P
JP
De Clercq
E
E
De Meester
I
I
Van Damme
J
J
D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes; D010446:Peptide Fragments / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction
D019380:Anti-HIV Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D010446:Peptide Fragments; D019718:Receptors, CXCR4; D018819:Dipeptidyl Peptidase 4