Role of endothelins on lymphocyte accumulation in allergic pleurisy.
Endothelins participate in different aspects of inflammatory reactions, including edema formation and eosinophil accumulation in allergic reaction. In this study, we demonstrated a role for endogenous endothelins in eosinophil and T lymphocyte recruitment and cytokine secretion in a murine model of allergic inflammation. Intrathoracic stimulation with endothelin-1 triggered a neutrophil accumulation at 4 h, concomitant with an increase of CD4+ and CD8+ T lymphocyte populations. Antigen challenge in sensitized animals leads to an increase in eosinophil and mononuclear cell numbers at 24 h. Treatment with ETA receptor antagonist (BQ123) inhibited antigen-induced eosinophil and mononuclear cell migration, whereas the selective ETB receptor antagonist BQ-788 was ineffective. The latter effect of BQ-123 was due to inhibition of CD4+ and CD8+ T lymphocytes. Treatment with BQ-123 also inhibited interleukin-5 levels in the exudate and plasma as well as intracellular staining of interleukin-4, interleukin-5, and interferon-gamma in CD4+ lymphocytes. These findings suggest that endogenous endothelins contribute to allergic inflammation by modulating lymphocyte recruitment and cytokine production.
Sampaio
A L
AL
Laboratory of Applied Pharmacology, FarManguinhos, FIOCRUZ, Rio de Janeiro, Brazil.
Rae
G A
GA
Henriques
M M
MM
D000818:Animals; D000077300:Bosentan; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D002634:Chemotaxis, Leukocyte; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D015759:Ionomycin / Q000494:pharmacology; D016131:Lymphocyte Subsets / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008985:Monensin / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010998:Pleurisy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D015848:Interleukin-5; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D013449:Sulfonamides; D015847:Interleukin-4; C086539:BQ 788; D015759:Ionomycin; D007371:Interferon-gamma; D010047:Ovalbumin; D008985:Monensin; D013755:Tetradecanoylphorbol Acetate; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)