Heat shock preconditioning inhibits CD4+ T lymphocyte activation in transplanted fatty rat livers.
Heat shock preconditioning (HPc) of fatty donor livers significantly increases recipient survival in rats. We investigated to what extent the blockade of Kupffer cells by gadolinium chloride (GdCl3) can mimic the effect of HPc and the involvement of liver CD4+ T lymphocytes in HPc. Fatty liver was experimentally induced in Lewis rats by a choline- and methionine-deficient diet. Fatty liver donors were pretreated with HPc (42.5 degrees C for 10 min), the Kupffer cell inhibitor GdCl3, or placebo (sham group). Donors were then harvested, stored in University of Wisconsin preservation solution for 12 h at 4 degrees C, and transplanted into normal syngeneic rats. Hepatic injury (alanine aminotransferase) and serum cytokines (interleukin-12p70, tumor necrosis factor-alpha, and interleukin-10) of recipients increased at 3 h, then decreased, and increased again at 24 h after transplantation. HPc treatment diminished both the early and later phases of this biphasic response and improved recipient survival. GdCl3 reduced these cytokines in the early but not the later phase and did not reduce neutrophil accumulation or improve the recipient survival. HPc, but not GdCl3 treatment, also reduced the number of liver CD4+ T lymphocytes and their interferon-gamma production. We conclude that HPc, but not GdCl3 treatment, prevents biphasic liver injury and the activation of liver CD4+ T lymphocytes in transplanted fatty donor livers.
Mokuno
Yasuji
Y
Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Berthiaume
François
F
Tanimura
Yoko
Y
Yarmush
Martin L
ML
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000601:surgery*; D005682:Gadolinium / Q000494:pharmacology; D006085:Graft Survival / Q000276:immunology*; D018869:Heat-Shock Response; D006979:Hyperthermia, Induced; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000276:immunology / Q000517:prevention & control; D019172:Transplantation Conditioning / Q000379:methods*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005682:Gadolinium; C038958:gadolinium chloride