title: Mast cell-derived TNF-alpha primes sensory nerve endings in a pulmonary hypersensitivity reaction.
abstract: TNF-alpha is a cytokine associated with inflammatory diseases, including asthma. Increased levels of TNF-alpha were found in the bronchoalveolar lavage fluid of mice undergoing a dinitrofluorobenzene (DNFB)-induced non-IgE-mediated pulmonary hypersensitivity reaction. We report in this work that TNF-alpha increases the susceptibility of sensory neurons to dinitrobenzene sulfonic acid (DNS) and capsaicin, leading to a tracheal vascular hyperpermeability response in DNFB-sensitized and DNS-challenged mice. mAb against TNF-alpha or the TNFR1 inhibited this hyperpermeability response in DNFB-sensitized and DNS-challenged mice. Furthermore, the hyperpermeability response after DNS challenge was abolished in DNFB-sensitized mast cell-deficient WBB6F(1)-W/W(V) mice. These animals showed a remarked decrease of TNF-alpha bronchoalveolar lavage fluid levels after a single DNS challenge. The hyperpermeability response after DNS challenge was regained in mast cell-deficient mice after mast cell reconstitution. These findings indicate a prominent role for TNF-alpha and its TNFR1 in the DNFB-induced tracheal hyperpermeability response. We propose that a priming effect of mast cell-derived TNF-alpha on the sensory neurons could be the mechanism of action of TNF-alpha in the vascular hyperpermeability response in tracheas of mice undergoing a pulmonary hypersensitivity reaction.
authors: Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3508 TB Utrecht, The Netherlands. A.H.vanHouwelingen@pharm.uu.nl
authors: Anneke H
authors: AH
authors: van Houwelingen
authors: Mirjam
authors: M
authors: Kool
authors: Saskia C A
authors: SC
authors: de Jager
authors: Frank A M
authors: FA
authors: Redegeld
authors: Dicky
authors: D
authors: van Heuven-Nolsen
authors: Aletta D
authors: AD
authors: Kraneveld
authors: Frans P
authors: FP
authors: Nijkamp
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD / Q000276:immunology; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D002211:Capsaicin / Q000008:administration & dosage; D004139:Dinitrofluorobenzene / Q000008:administration & dosage / Q000276:immunology; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007117:Immunization, Secondary; D007275:Injections, Intravenous; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009411:Nerve Endings / Q000187:drug effects / Q000276:immunology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014132:Trachea / Q000187:drug effects / Q000276:immunology / Q000294:innervation; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001557:Benzenesulfonates; D006241:Haptens; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C007488:dinitrobenzenesulfonic acid; D004139:Dinitrofluorobenzene; D002211:Capsaicin