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 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.
Shibata
Futoshi
F
fshibata@ms.toyama-mpu.ac.jp
Konishi
Kiyoshi
K
Nakagawa
Hideo
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054360:Chemokine CXCL1; D018925:Chemokines / Q000494:pharmacology; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D023063:Receptors, Interleukin-8B / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; C513294:Cxcl3 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D023063:Receptors, Interleukin-8B; D002118:Calcium