Mechanisms underlying the inhibitory effects of tachykinin receptor antagonists on eosinophil recruitment in an allergic pleurisy model in mice.
The activation of tachykinin NK receptors by neuropeptides may induce the recruitment of eosinophils in vivo. The aim of the present study was to investigate the effects and underlying mechanism(s) of the action of tachykinin receptor antagonists on eosinophil recruitment in a model of allergic pleurisy in mice. Pretreatment of immunized mice with capsaicin partially prevented the recruitment of eosinophils after antigen challenge, suggesting the potential contribution of sensory nerves for the recruitment of eosinophils Local (10-50 nmol per pleural cavity) or systemic (100-300 nmol per animal) pretreatment with the tachykinin NK1 receptor antagonist SR140333 prevented the recruitment of eosinophils induced by antigen challenge of immunized mice. Neither tachykinin NK2 nor NK3 receptor antagonists suppressed eosinophil recruitment. Pretreatment with SR140333 failed to prevent the antigen-induced increase of interleukin-5 concentrations in the pleural cavity. Similarly, SR140333 failed to affect the bone marrow eosinophilia observed at 48 h after antigen challenge of immunized mice. SR140333 induced a significant increase in the concentrations of antigen-induced eotaxin at 6 h after challenge. Antigen challenge of immunized mice induced a significant increase of Leucotriene B4 (LTB4) concentrations at 6 h after challenge. Pretreatment with SR140333 prevented the antigen-induced increase of LTB4 concentrations. Our data suggest an important role for NK1 receptor activation with consequent LTB4 release and eosinophil recruitment in a model of allergic pleurisy in the mouse. Tachykinins appear to be released mainly from peripheral endings of capsaicin-sensitive sensory neurons and may act on mast cells to facilitate antigen-driven release of LTB4.
Departamento Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Ana Leticia
AL
Alessandri
Vanessa
V
Pinho
Danielle G
DG
Souza
Maria Salete de A
MS
Castro
Andre
A
Klein
Mauro M
MM
Teixeira
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010880:Piperidines / Q000494:pharmacology; D010998:Pleurisy / Q000276:immunology / Q000378:metabolism*; D011812:Quinuclidines / Q000494:pharmacology; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
D010880:Piperidines; D011812:Quinuclidines; D018039:Receptors, Tachykinin; C085215:SR 140333