title: TNF alpha is localized to nasal mucosal mast cells and is released in acute allergic rhinitis.
abstract: Allergic mucosal inflammation is characterized by tissue infiltration with eosinophils, and associated activation of mast cells and T lymphocytes. Tumour necrosis factor (TNF) alpha/cachectin is a candidate cytokine relevant to the pathogenesis of these events through its capacity to upregulate the expression of endothelial cell adhesion molecules, mediate granulocyte chemoattraction, and activate eosinophils, mast cells and T cells. To investigate the presence and localization of TNF alpha in the nasal mucosa in allergic rhinitis, nasal biopsies from perennial rhinitic (n = 13) and non-rhinitic volunteers (n = 11) were embedded in glycol methacrylate and immunostained with a monoclonal antibody directed against TNF alpha, and adjacent 2 microns sections stained for tryptase, CD3 and eosinophil cationic protein. This identified positive immunostaining for TNF alpha in the submucosa of both the rhinitic and normal subjects (median cell counts 13 and 23 cells/mm2 respectively, P = 0.24) with cellular localization to mast cells but not to T-lymphocytes or eosinophils. In a subsequent study of seven atopic subjects, nasal allergen challenge produced increases in lavage levels of histamine and albumin, which was associated with significant release of TNF alpha as early as 2 min post-allergen when compared with the saline control day (P = 0.05). This difference was also apparent when studying the area under the curve both at 30 and 60 min post-challenge t-test (P = 0.015 and 0.02 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Immunopharmacology Group, Southampton University, UK.
authors.forename: P
authors.initials: P
authors.lastname: Bradding
authors.forename: R
authors.initials: R
authors.lastname: Mediwake
authors.forename: I H
authors.initials: IH
authors.lastname: Feather
authors.forename: J
authors.initials: J
authors.lastname: Madden
authors.forename: M K
authors.initials: MK
authors.lastname: Church
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: P H
authors.initials: PH
authors.lastname: Howarth
mesh_terms: D000328:Adult; D000418:Albumins / Q000378:metabolism; D001706:Biopsy; D053818:Chymases; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D017817:Nasal Lavage Fluid / Q000737:chemistry; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D012697:Serine Endopeptidases / Q000378:metabolism; D053802:Tryptases; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D000418:Albumins; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases