Differential regulation of the release of tumor necrosis factor-alpha and of eicosanoids by mast cells in rat airways after antigen challenge

Mediators Inflamm. 2003 Aug;12(4):237-46. doi: 10.1080/09629350310001599684.

Abstract

Background: Rat trachea display a differential topographical distribution of connective tissue mast cells (CTMC) and mucosal mast cells (MMC) that may imply regional differences in the release of allergic mediators such as tumor necrosis factor-alpha (TNF-alpha) and eicosanoids.

Aim: To evaluate the role of CTMC and MMC for release of TNF-alpha and eicosanoids after allergenic challenge in distinct segments of rat trachea.

Materials and methods: Proximal trachea (PT) and distal trachea (DT) from ovalbumin (OVA)-sensitized rats, treated or not with compound 48/80 (48/80) or dexamethasone, were incubated in culture medium. After OVA challenge, aliquots were collected to study release of TNF-alpha and eicosanoids.

Results: Release of TNF-alpha by PT upon OVA challenge peaked at 90 min and decayed at 6 and 24 h. Release from DT peaked at 30-90 min and decayed 6 and 24 h later. When CTMC were depleted with 48/80, OVA challenge exacerbated the TNF-alpha release by PT at all time intervals, while DT exacerbated TNF-alpha levels 6 and 24 h later only. Dexamethasone reduced TNF-alpha production after 90 min of OVA challenge in PT and at 3 and 6h in DT. OVA challenge increased prostaglandin D2) in DT and leukotriene B4 in both segments but did not modify prostaglandin E2 and leukotriene C4 release.

Conclusion: OVA challenge induces TNF-alpha release from MMC, which is negatively regulated by CTMC. The profile of TNF-alpha and eicosanoids depends on the time after OVA challenge and of the tracheal segment considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchial Provocation Tests*
  • Dexamethasone / pharmacology
  • Eicosanoids / metabolism*
  • Glucocorticoids / pharmacology
  • Male
  • Mast Cells / cytology
  • Mast Cells / drug effects
  • Mast Cells / immunology
  • Mast Cells / metabolism*
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Rats
  • Rats, Wistar
  • Trachea / cytology
  • Trachea / immunology*
  • Trachea / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*
  • p-Methoxy-N-methylphenethylamine / pharmacology

Substances

  • Eicosanoids
  • Glucocorticoids
  • Tumor Necrosis Factor-alpha
  • p-Methoxy-N-methylphenethylamine
  • Dexamethasone
  • Ovalbumin