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Tumour necrosis factor‐alpha and leukotriene B 4 mediate the neutrophil migration in immune inflammation
Author(s) -
Canetti C,
Silva J S,
Ferreira S H,
Cunha F Q
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704403
Subject(s) - tumor necrosis factor alpha , leukotriene b4 , ovalbumin , inflammation , chemotaxis , immunology , immune system , receptor , chemistry , medicine , biology , endocrinology
We investigated the mediators responsible for neutrophil migration induced by ovalbumin (OVA) in immunized mice and the mechanisms involved in their release. OVA administration promoted dose‐ and time‐dependent neutrophil migration in immunized, but not in non‐immunized mice, which was mediated by leukotriene B 4 (LTB 4 ) and tumour necrosis factor (TNF)α, since it was inhibited by LTB 4 synthesis inhibitor (MK 886) or by LTB 4 receptor antagonist (CP 105,696), by dexamethasone and by antiserum to TNFα (82, 85, 63 and 87%, respectively). Confirming TNFα involvement, OVA challenge in immunized p55 TNF receptor deficient mice (p55 −/− ) did not promote neutrophil migration (control: 2.90±0.68; p55 −/− : 0.92±0.23×10 6 neutrophils cavity −1 ). OVA‐stimulated peritoneal cells from immunized mice released a neutrophil chemotactic factor which mimicked, in naive mice, neutrophil migration induced by OVA. Supernatant chemotactic activity is due to TNFα and LTB 4 , since its release was inhibited by MK 886 (93%) and dexamethasone (90%), and significant amounts of these mediators were detected. TNFα and LTB 4 released by OVA challenge seem to act through a sequential mechanism, since MK 886 inhibited (88%) neutrophil migration induced by TNFα. Moreover, peritoneal cells stimulated with TNFα released LTB 4 . CD 4 + T cells are responsible for TNFα release, because the depletion of this subset prevented the release of TNFα (control: 400±25; immunized: 670±40; CD 4 + depleted: 435±18 pg ml −1 ). In conclusion, neutrophil migration induced by OVA depends on TNFα released by CD 4 + cells, which acts through an LTB 4 ‐dependent mechanism.British Journal of Pharmacology (2001) 134 , 1619–1628; doi: 10.1038/sj.bjp.0704403