title: Mast cells play a key role in the development of late airway hyperresponsiveness through TNF-alpha in a murine model of asthma.
abstract: We have investigated the role of TNF-alpha in mast cell-mediated late airway hyperresponsiveness (AHR) using mast cell-deficient WBB6F1-W/W(v) (W/W(v)) mice in a murine model of asthma, which exhibits a biphasic increase in AHR. TNF-alpha levels in the airway and magnitude of late AHR in response to airway allergen challenge were severely impaired in W/W(v) mice compared to their littermates. In addition to TNF-alpha, cytosolic phospholipase A(2) (cPLA(2)) phosphorylation and enzymatic activity in the lungs were also impaired in W/W(v) mice. Either anti-TNF-alpha antibody or an inhibitor of cPLA(2) abolished late AHR in congeneic +/+ mice. Intratracheal administration of TNF-alpha resulted in increases in late AHR, cPLA(2 )phosphorylation, cPLA(2 )activity, and phosphorylation of mitogen-activated protein kinases. Mast cell replacement restored airway TNF-alpha level, cPLA(2 )phosphorylation and enzymatic activity in the lungs as well as late AHR in W/W(v) mice. These data indicate that mast cells play a key role in the development of late AHR through liberation of TNF-alpha.
authors: Department of Immunology, Chonbuk National University Medical School, Chonju, Republic of Korea.
authors: Young-Suk
authors: YS
authors: Kim
authors: Hyun-Mi
authors: HM
authors: Ko
authors: Nam-In
authors: NI
authors: Kang
authors: Chang-Ho
authors: CH
authors: Song
authors: Xin
authors: X
authors: Zhang
authors: Woo-Chan
authors: WC
authors: Chung
authors: Jae-Hong
authors: JH
authors: Kim
authors: In-Hak
authors: IH
authors: Choi
authors: Young-Min
authors: YM
authors: Park
authors: Gi-Young
authors: GY
authors: Kim
authors: Shun-Young
authors: SY
authors: Im
authors: Hern-Ku
authors: HK
authors: Lee
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha