Tumour necrosis factor-alpha and leukotriene B(4) mediate the neutrophil migration in immune inflammation.
1. We investigated the mediators responsible for neutrophil migration induced by ovalbumin (OVA) in immunized mice and the mechanisms involved in their release. 2. 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)alpha, 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 TNFalpha (82, 85, 63 and 87%, respectively). Confirming TNFalpha 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 x 10(6) neutrophils cavity(-1)). 3. OVA-stimulated peritoneal cells from immunized mice released a neutrophil chemotactic factor which mimicked, in naive mice, neutrophil migration induced by OVA. 4. Supernatant chemotactic activity is due to TNFalpha and LTB(4), since its release was inhibited by MK 886 (93%) and dexamethasone (90%), and significant amounts of these mediators were detected. 5. TNFalpha and LTB(4) released by OVA challenge seem to act through a sequential mechanism, since MK 886 inhibited (88%) neutrophil migration induced by TNFalpha. Moreover, peritoneal cells stimulated with TNFalpha released LTB(4). 6. CD(4)(+) T cells are responsible for TNFalpha release, because the depletion of this subset prevented the release of TNFalpha (control: 400 +/- 25; immunized: 670 +/- 40; CD(4)(+) depleted: 435 +/- 18 pg ml(-1)). 7. In conclusion, neutrophil migration induced by OVA depends on TNFalpha released by CD(4)(+) cells, which acts through an LTB(4)-dependent mechanism.
Canetti
C
C
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Silva
J S
JS
Ferreira
S H
SH
Cunha
F Q
FQ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005620:Freund's Adjuvant / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D007975:Leukotriene B4 / Q000378:metabolism / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D010047:Ovalbumin; D005620:Freund's Adjuvant