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 chemokine eotaxin has been characterized as an important mediator in allergic reactions because it selectively attracts eosinophils, Th2 lymphocytes, and basophils. Human eotaxin has a penultimate proline, indicating that it might be a substrate for dipeptidyl-peptidase IV (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-truncated 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 chemotaxis toward intact eotaxin. In addition, HIV-2 infection of CC chemokine receptor 3-transfected cells was inhibited to a similar extent by eotaxin and eotaxin(3-74). Thus, CD26/DPP IV differently regulates the chemotactic and antiviral potencies of eotaxin by the removal of two NH2-terminal residues. This physiological processing may be an important down-regulatory mechanism, limiting eotaxin-mediated inflammatory responses.
Struyf
S
S
Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Belgium.
Proost
P
P
Schols
D
D
De Clercq
E
E
Opdenakker
G
G
Lenaerts
J P
JP
Detheux
M
M
Parmentier
M
M
De Meester
I
I
Scharpé
S
S
Van Damme
J
J
D019380:Anti-HIV Agents / Q000494:pharmacology*; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology*; D015536:Down-Regulation / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology / Q000502:physiology; D006801:Humans; D006868:Hydrolysis; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000276:immunology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism* / Q000502:physiology; D015728:Receptors, HIV / Q000037:antagonists & inhibitors; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000276:immunology
D019380:Anti-HIV Agents; C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D010446:Peptide Fragments; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D015728:Receptors, HIV; D018819:Dipeptidyl Peptidase 4