Role of Spleen-Derived Macrophages and Involvement of Superoxide Anion in Propionibacterium acne-Elicited and Lipopolysaccharide-Induced Liver Injury of Rats.

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Intravenous administration of Propionibacterium acnes (P.acnes, 16mg/kg) followed by a small amount of lipopolysaccharide (LPS, 200μg/kg) one week later caused severe liver injury in rats. In in vivo studies, the contribution of spleen-derived macrophages to the liver injury in this model was investigated. Splenectomized rats had lower levels of plasma tumor necrosis factor α (TNFα), growth related oncogene/cytokine-induced neutrophil chemoattractant 1 (GRO/CINC-1), purine nucleoside phosphorylase (PNP) and aspartate aminotransferase (AST) than non-splenectomized rats. In organ perfusion studies, the hypothesis that macrophage-derived reactive oxygen species mediate the liver injury was verified. Leakage of PNP into the perfusate immediately followed release of superoxide anion (O2-) which was measured by a chemiluminescence technique using a Cypridina luciferin analogue (MCLA) as a highly sensitive chemiluminescence probe for O2-. Increase of TNFα, GRO/CINC-1 and AST levels in the perfusate lagged behind PNP release. Simultaneous administration of superoxide dismutase and deferoxamine significantly suppressed PNP and AST release. From these results, we believe that spleen-derived macrophages have an important pathological role in P.acnes-LPS-induced liver injury in rats via release of O2-.