Neutrophil migration induced by IL-8-activated mast cells is mediated by CINC-1.
The aim of this study was to characterize the mediators released by mast cells responsible for IL-8-induced neutrophil migration. It was observed that IL-8 induces a dose-dependent neutrophil migration into peritoneal cavity of rats, but not into air-pouch cavity in which resident mast cells are not present. The transference of peritoneal mast cells to the air-pouch renders this cavity responsive to IL-8. The neutrophil migration induced by IL-8 into the peritoneal cavity was not observed when the peritoneal-resident mast cells were depleted by compound 48/80 or distilled water treatment. Confirming the importance of mast cells, IL-8-stimulated mast cells supernatant induced significant neutrophil migration when injected into peritoneal and air-pouch cavities. The IL-8-induced neutrophil migration was observed not to be dependent on LTB(4), prostaglandins or TNF-alpha, since MK886, indomethacin or thalidomide were unable to block the IL-8-induced neutrophil accumulation 'in vivo' or the release of neutrophil chemotactic factor "in vitro" by IL-8-stimulated mast cells. However, dexamethasone, an inhibitor of the synthesis of pro-inflammatory cytokines, blocked the neutrophil migration induced by IL-8 "in vivo" and also inhibited the release of the neutrophil chemotactic factor by IL-8-stimulated mast cells. Moreover, the incubation of IL-8-stimulated mast cells supernatant with antibody against cytokine-induced neutrophil chemoattractant 1 (CINC-1), but not against TNF-alpha or IL-1beta, inhibited its neutrophil chemotactic activity. Furthermore, we found a significant amount of CINC-1 in this supernatant. In conclusion, we demonstrated that the neutrophil migration induced by IL-8 is dependent on CINC-1 release from mast cells.
Ramos
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Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo-USP, Avenida Bandeirantes 3900, Ribeirão Preto, Sao Paulo 14049-900, Brazil.
Heluy-Neto
N E
NE
Ribeiro
R A
RA
Ferreira
S H
SH
Cunha
F Q
FQ
D000818:Animals; D054360:Chemokine CXCL1; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D003907:Dexamethasone / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D016209:Interleukin-8 / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000494:pharmacology; D002722:Chlorobenzenes
D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D003907:Dexamethasone; D007211:Indoles; D007213:Indomethacin; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D013792:Thalidomide; C513297:Cxcl1 protein, rat; C060893:MK-886; D002722:Chlorobenzenes