Intrinsic resistance of hepatocytes to complement-mediated injury.
When activated on or in the vicinity of cells, complement usually causes loss of function and sometimes cell death. Yet the liver, which produces large amounts of complement proteins, clears activators of complement and activated complexes from portal blood without obvious injury or impaired function. We asked whether and to what extent hepatocytes resist injury and loss of function mediated by exposure to complement. Using cells isolated from porcine livers as a model system, we found that, in contrast to endothelial cells, hepatocytes profoundly resist complement-mediated lysis and exhibit normal synthetic and conjugative functions when complement is activated on their surface. The resistance of hepatocytes to complement-mediated injury was not a function of cell surface control of the complement cascade but rather an intrinsic resistance of the cells dependent on the PI3K/Akt pathway. The resistance of hepatocytes to complement might be exploited in developing approaches to the treatment of hepatic failure or more broadly to the treatment of complement-mediated disease.
Koch
Cody A
CA
Transplantation Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Kanazawa
Akiyoshi
A
Nishitai
Ryuta
R
Knudsen
Bruce E
BE
Ogata
Kiyoshi
K
Plummer
Timothy B
TB
Butters
Kim
K
Platt
Jeffrey L
JL
D000818:Animals; D000910:Antibodies, Heterophile / Q000378:metabolism; D001666:Binding Sites, Antibody; D002478:Cells, Cultured; D003167:Complement Activation / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000502:physiology*; D003165:Complement System Proteins / Q000378:metabolism / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013552:Swine
D000910:Antibodies, Heterophile; D003169:Complement Inactivator Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D003165:Complement System Proteins