Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 134, Issue 8, Pages 1619-1628Publisher
WILEY
DOI: 10.1038/sj.bjp.0704403
Keywords
immune inflammation; LTB4; TNF alpha; cytokines; neutrophil migration
Categories
Ask authors/readers for more resources
1 We investigated the mediators responsible for neutrophil migration induced by ovalburnin (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 (LTB4) and tumour necrosis factor (TNF)(,alpha) since it was inhibited by LTB4 synthesis inhibitor (MK 886) or by LTB4 receptor antagonist (CP 105,696), by dexamethasone and by antiserum. to TNF alpha (82, 85, 63 and 87%, respectively). Confirming TNF alpha 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 TNF alpha and LTB4, since its release was inhibited by MK 886 (93%) and dexamethasone (90%), and significant amounts of these mediators were detected. 5 TNF alpha and LTB4 released by OVA challenge seem to act through a sequential mechanism, since MK 886 inhibited (88%) neutrophil migration induced by TNF alpha. Moreover, peritoneal cells stimulated with TNF alpha released LTB4. 6 CD4+ T cells are responsible for TNF alpha release, because the depiction of this subset prevented the release of TNF alpha (control: 400 +/- 25; immunized: 670 +/- 40; CD4+ depleted: 435 +/- 18 pg ml(-1)). 7 In conclusion, neutrophil migration induced by OVA depends on TNF alpha released by CD4+ cells, which acts through an LTB4-dependent mechanism.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available