Chemokine Receptor CXCR2 Activates Distinct Pathways for Chemotaxis and Calcium Mobilization

Rat cytokine-induced neutrophil chemoattractant-3 (CINC-3) has neutrophil chemotactic activity comparable with that of CINC-1 and CINC-2, but induces calcium mobilization more potently than CINC-1 and CINC-2. However, only one CINC receptor, CXCR2, has been found in rat neutrophils. Therefore we att...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2002, Vol.25(9), pp.1217-1219
Main Authors: Shibata, Futoshi, Konishi, Kiyoshi, Nakagawa, Hideo
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Calcium - metabolism
calcium mobilization
chemokine
Chemokine CXCL1
Chemokines - pharmacology
Chemokines, CXC
Chemotactic Factors - pharmacology
chemotaxis
Chemotaxis - drug effects
Chemotaxis - physiology
cytokine-induced neutrophil chemoattractant (CINC)
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunobiology
Intercellular Signaling Peptides and Proteins - pharmacology
macrophage inflammatory protein-2 (MIP-2)
Male
Myeloid cells: ontogeny, maturation, markers, receptors
Neutrophils - drug effects
Neutrophils - metabolism
pertussis toxin
Polynuclears
Rats
Rats, Wistar
Receptors, Interleukin-8B - agonists
Receptors, Interleukin-8B - metabolism
Signal Transduction - drug effects
Signal Transduction - physiology
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Summary:Rat cytokine-induced neutrophil chemoattractant-3 (CINC-3) has neutrophil chemotactic activity comparable with that of CINC-1 and CINC-2, but induces calcium mobilization more potently than CINC-1 and CINC-2. However, only one CINC receptor, CXCR2, has been found in rat neutrophils. Therefore we attempted to determine the biochemical basis for the differences in neutrophil responses to CINC-1/-2 versus CINC-3. Both chemotactic activity and calcium mobilization induced by CINC-3 were desensitized by a 100-fold excess of CINC-1, which was consistent with our previous results showing that CINC-1 has 70-fold lower affinity to the receptor on rat neutrophils than CINC-3. Desensitization appeares to be reflected by the affinity of the ligands to the receptor. CINC-1- and CINC-3-induced chemotaxis was sensitive to inhibition by pertussis toxin, whereas calcium mobilization induced by CINC-1 and CINC-3 was insensitive. These results suggest that CINCs induce neutrophil chemotaxis and calcium mobilization through distinct G-proteins with different efficiency.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.25.1217