Production and release of endothelin-1 from the gut and spleen in portal hypertension due to cirrhosis.
This study was aimed to evaluate the source of endothelin-1 (ET-1) in cirrhotic patients. ET-1 is implicated in the pathogenesis of portal hypertension. However, the mechanism and source for increased plasma ET-1 in cirrhotic patients are still obscure. Plasma ET-1 levels in systemic (SV), superior mesenteric (SMV), and splenic venous (SPV) blood were measured in 23 patients with cirrhosis and 8 controls with normal liver. Fourteen removed spleens were immunohistochemically studied for ET-1, CD34, CD68, and CD20. In situ hybridization was done to localize ET-1 messenger RNA (mRNA). In cirrhosis, ET-1 levels in both SMV and SPV were higher than in SV. ET-1 in SV and SPV were significantly higher in cirrhotic patients than in control patients. Three groups of cells in the spleen expressed both protein and mRNA of ET-1: endothelial cells in the sinus, which were also stained for CD34; cells in the germinal center; and cells in the marginal zone of lymphoid sheaths and follicles, which were also stained for CD20 but not for CD34 and CD68. The ET-1 concentration released from the spleen was in parallel with the grade of ET-1 expression in the spleen. The spleen is one of the major sites of ET-1 release in cirrhotic patients. Endothelial cells of the splenic sinus and possibly B lymphocytes in the germinal center and marginal zone of lymphoid sheaths and follicles seem to be the sites of ET-1 production in the spleen.
Nagasue
N
N
Second Department of Surgery, Shimane Medical University, Izumo, Japan.nigeka1@shimane-med.ac.jp
Dhar
D K
DK
Yamanoi
A
A
Emi
Y
Y
Udagawa
J
J
Yamamoto
A
A
Tachibana
M
M
Kubota
H
H
Kohno
H
H
Harada
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000378:metabolism*; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000503:physiopathology; D013154:Spleen / Q000378:metabolism*; D014690:Venous Pressure; D000097382:CD68 Molecule
D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D019332:Endothelin-1; C067980:CD68 antigen, human; D000097382:CD68 Molecule