Endothelin-1 production during the acute chest syndrome in sickle cell disease.
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.
Hammerman
S I
SI
Pulmonary Center, Boston University School of Medicine, MA 02118, USA.
Kourembanas
S
S
Conca
T J
TJ
Tucci
M
M
Brauer
M
M
Farber
H W
HW
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
D019332:Endothelin-1; D012333:RNA, Messenger; D012313:RNA