title: Kupffer cell-mediated lymphocyte apoptosis: a PGE2-dependent mechanism of portal venous transfusion-induced immunosuppression?
abstract: BACKGROUND
  Kupffer cells, after exposure to alloantigen via the portal vein, mediate an immunosuppressive effect involving enhanced production of PGE2. We hypothesize that up-regulation of Kupffer cell CoA-independent transacylase (CoA-IT) by portal venous transfusion (PVT) is a possible mechanism of increased PGE2 production. Additionally, enhanced lymphocyte apoptosis, a process known to be macrophage dependent and facilitated by PGE2, is postulated as a possible mechanism of PVT-induced, Kupffer cell-mediated immunosuppression.
  
  
  METHODS
  Lewis rat Kupffer cells were isolated after portal venous infusion with 1 ml of Wistar-Firth blood (PVT) or saline (PV sal). Kupffer cell PGE2 production and CoA-IT activity was assessed. Lymphocyte apoptosis after exposure to PVT or PV sal-treated Kupffer cells was also assessed by flow cytometry.
  
  
  RESULTS
  PVT-treated Kupffer cells produced significantly more PGE2 and had increased CoA-IT activity when compared to PV sal-treated Kupffer cells. Treatment of Kupffer cells with a selective inhibitor of CoA-IT significantly decreased PVT-induced Kupffer cell PGE2 production. Increased lymphocyte apoptosis was observed after coculture with PVT-treated Kupffer cells compared to PV sal-treated cells.
  
  
  CONCLUSIONS
  PVT increases Kupffer cell PGE2 production via increased CoA-IT activity and induces Kupffer cell-mediated lymphocyte apoptosis. Lymphocyte apoptosis facilitated by Kupffer cells within the hepatic sinusoid may be an important mechanism of PVT-induced immunosuppression in organ transplantation.
authors.affiliation: Department of Surgery, University of California, Davis, Sacramento, California 95817, USA. rvperez@ucdavis.edu
authors.forename: R
authors.initials: R
authors.lastname: Perez
authors.forename: J
authors.initials: J
authors.lastname: Johnson
authors.forename: J D
authors.initials: JD
authors.lastname: Winkler
authors.forename: S
authors.initials: S
authors.lastname: Rudich
authors.forename: L
authors.initials: L
authors.lastname: Carter
authors.forename: S
authors.initials: S
authors.lastname: Katznelson
authors.forename: J B
authors.initials: JB
authors.lastname: German
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001803:Blood Transfusion; D015232:Dinoprostone / Q000378:metabolism*; D005434:Flow Cytometry; D007165:Immunosuppression Therapy; D007728:Kupffer Cells / Q000201:enzymology / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D011169:Portal Vein; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF
chemical_list: D000217:Acyltransferases; C039766:arachidonyl transacylase; D015232:Dinoprostone