Endothelin-1 potentiates smoke-induced acute lung inflammation.
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."
Bhavsar
Tapan M
TM
School of Pharmacy and Allied Health Sciences, St John's University, New York, New York, USA.
Liu
Xingjian
X
Cerreta
Joseph M
JM
Liu
Ming
M
Cantor
Jerome O
JO
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*
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