title: Endothelin-1 production during the acute chest syndrome in sickle cell disease.
abstract: To investigate the role of the endothelial-derived vasoactive mediator endothelin (ET-1) in the acute chest syndrome (ACS), we incubated bovine pulmonary artery endothelial cells (BPAEC) with red blood cells (equivalent to a hematocrit of 20%) and/or autologous plasma (1:10 dilution) from two patients during ACS and during routine clinic visits. Cellular RNA was analyzed for ET-1 transcripts by Northern analysis and ET-1 protein levels in BPAEC supernatants and in plasma measured by radioimmunoassay. ET-1 mRNA expression and protein levels increased in BPAEC exposed to plasma obtained during ACS; in contrast, exposure to plasma obtained during routine clinic visits did not alter BPAEC ET-1 mRNA expression or protein levels. Plasma ET-1 level was elevated during ACS, decreased during resolution, and remained slightly elevated during routine clinic visits. Plasma obtained from one patient 4 d prior to hospitalization for vasoocclusive crisis contained the highest ET-1 level and markedly increased BPAEC ET-1 mRNA expression and protein levels. In both patients, BPAEC ET-1 mRNA and protein expression in vitro and plasma ET-1 levels in vivo correlated with stage of disease and occurred in the absence of direct erythrocyte contact in vitro. These observations suggest that ET-1 production contributes to development of ACS.
authors.affiliation: Pulmonary Center, Boston University School of Medicine, MA 02118, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Hammerman
authors.forename: S
authors.initials: S
authors.lastname: Kourembanas
authors.forename: T J
authors.initials: TJ
authors.lastname: Conca
authors.forename: M
authors.initials: M
authors.lastname: Tucci
authors.forename: M
authors.initials: M
authors.lastname: Brauer
authors.forename: H W
authors.initials: HW
authors.lastname: Farber
mesh_terms: D000208:Acute Disease; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications; D000818:Animals; D002417:Cattle; D019332:Endothelin-1 / Q000032:analysis / Q000097:blood*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000097:blood* / Q000209:etiology; D011651:Pulmonary Artery / Q000737:chemistry; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D012313:RNA