Immunosuppressive mechanism of 15-deoxyspergualin on sinusoidal lining cells in swine liver transplantation: Suppression of MHC class II antigens and interleukin-1 production

Abstract

To elucidate the precise mechanism of action of 15-deoxyspergualin (DSG) in swine liver transplantation, the expression of MHC class II antigens (Ia) on hepatic sinusoidal lining cells (SLC) and their production of interleukin-1 (IL-1) were examined. In our previous study, we isolated sinusoidal endothelial cells (SEC) and Kupffer cells (KC) by enzymatic digestion and centrifugal elutriation, and demonstrated that both SEC and KC present alloantigens effectively and generated IL-1 in response to allogenic or lipopolysaccharide stimulation. Animals were divided into three groups: group 1, nontransplanted normal controls ( n = 3); group 2, no immunosuppressive treatment following liver transplantation ( n = 5); group 3, DSG (0.8 mg/kg/day) intravenously for 7 days following liver transplantation ( n = 5). At 1 week after transplantation, the three liver grafts in groups 2 and 3 were processed for the study of Ia expression and IL-1 production on SEC and KC. The expression of Ia was detected in 21.5 ± 4.7% of SEC and 24.3 ± 11.1% of KC in group 1. In group 3, Ia expression was suppressed compared with group 2, being 3.6 ± 2.8% versus 22.0 ± 2.8% for SEC ( P < 0.02) and 15.5 ± 11.3% versus 24.3 ± 7.1% for KC. IL-1 production by SEC and KC was respectively 11,483 ± 3311 cpm and 9077 ± 2161 cpm in group 1. In group 3, IL-1 production was inhibited compared with that in group 2, being 7190 ± 883 cpm versus 19.297 ± 5182 cpm for SEC ( P < 0.05) and 16,130 ± 3769 cpm versus 25,857 ± 3963 cpm for KC. In addition, we demonstrated histologically that DSG suppressed liver allograft rejection.