Participation of endogenous endothelins in delayed eosinophil and neutrophil recruitment in mouse pleurisy.
OBJECTIVE
Investigate the role of endothelins in leukocyte recruitment in allergic and non allergic inflammation.


METHODS
Pleurisy was induced in mice by intrathoracic injection of ovalbumin (OVA; in sensitized animals), E. coli LPS, carrageenan, Mycobacterium bovis (BCG) or zymosan. Animals were treated with BQ-123 or BQ-788 (1.5-150 pmol/cavity), or intravenously with bosentan (30 mg/kg).


RESULTS
None of the ET receptor antagonists modified early neutrophil recruitment (at 4 h) induced by OVA, LPS, carrageenan, BCG or zymosan or plasma leakage caused by carrageenan or zymosan. Mononuclear and eosinophil accumulation triggered by OVA were reduced by BQ-123 (150 pmol/cavity) or bosentan (68 and 43% inhibition of eosinophilia), but unaffected by BQ-788. BQ-123 and bosentan also inhibited LPS increases in neutrophil (by 67 and 40%) and eosinophil (by 63 and 74%) at 24 h.


CONCLUSIONS
Endothelins, acting via ETA receptors, play a role in late eosinophil and neutrophil accumulation (24 h), but not in the acute (4 h) neutrophilic response.
Sampaio
A L
AL
Laboratório de Farmacologia Aplicada, Instituto de Tecnologia em Fármacos - FARMANGUINHOS - Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
Rae
G A
GA
Henriques
M G
MG
D000818:Animals; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology*; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010998:Pleurisy / Q000139:chemically induced / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D008070:Lipopolysaccharides; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D011506:Proteins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C086539:BQ 788; D010047:Ovalbumin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)