title: Endothelin-1 potentiates smoke-induced acute lung inflammation.
abstract: The current study examined the role of endothelin-1 (ET-1) in mediating acute lung inflammation induced by short-term cigarette smoke exposure. Hamsters received intraperitoneal injections of ET-1, followed by a 2-hour period of smoke exposure, for 3 consecutive days. The lungs were then evaluated for inflammatory changes, using the following parameters: (1) lung histopathology, (2) neutrophil content of bronchoalveolar lavage fluid (BALF), (3) percent tumor necrosis factor receptor 1 (TNFR1)-labeled BALF macrophages, and (4) alveolar septal cell apoptosis. Results indicate that ET-1 significantly amplified the effect of smoke on each of these inflammatory markers and that these responses could be blocked by pretreatment with a novel endothelin receptor A antagonist, HJP272. In particular, exogenous ET-1 induced a marked increase in BALF neutrophils, consistent with a role for this mediator as an inflammatory cell "gatekeeper."
authors.affiliation: School of Pharmacy and Allied Health Sciences, St John's University, New York, New York, USA.
authors.forename: Tapan M
authors.initials: TM
authors.lastname: Bhavsar
authors.forename: Xingjian
authors.initials: X
authors.lastname: Liu
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Cerreta
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Jerome O
authors.initials: JO
authors.lastname: Cantor
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D006224:Cricetinae; D019332:Endothelin-1 / Q000494:pharmacology*; D006912:Hydroxyquinolines / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008647:Mesocricetus; D011014:Pneumonia / Q000209:etiology*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: C532839:3-(3-carboxybenzyl)-1-((6-ethylbenzo(d)(1,3)dioxol-5-yl)methyl)-6-hydroxy-4-oxo-1,4-dihydroquinoline-2-carboxylic acid; D019332:Endothelin-1; D006912:Hydroxyquinolines; D047888:Receptors, Tumor Necrosis Factor, Type I; D014028:Tobacco Smoke Pollution