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.
MeSH terms
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Administration, Topical
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antigens, CD / immunology
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Benzenesulfonates / administration & dosage
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Benzenesulfonates / immunology
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Bronchoalveolar Lavage Fluid / chemistry
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Bronchoalveolar Lavage Fluid / immunology
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Capillary Permeability / drug effects
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Capillary Permeability / immunology
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Capsaicin / administration & dosage
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Dinitrofluorobenzene / administration & dosage
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Dinitrofluorobenzene / immunology
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Haptens / administration & dosage
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Haptens / immunology
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Immunization, Secondary
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Injections, Intravenous
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Male
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Mast Cells / immunology*
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Mast Cells / metabolism
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Mast Cells / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Mutant Strains
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Nerve Endings / drug effects
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Nerve Endings / immunology*
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Neurons, Afferent / drug effects
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Neurons, Afferent / immunology*
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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Respiratory Hypersensitivity / chemically induced
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Respiratory Hypersensitivity / immunology*
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Respiratory Hypersensitivity / metabolism
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Respiratory Hypersensitivity / pathology
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Trachea / drug effects
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Trachea / immunology
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Trachea / innervation
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Benzenesulfonates
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Haptens
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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Tumor Necrosis Factor-alpha
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dinitrobenzenesulfonic acid
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Dinitrofluorobenzene
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Capsaicin