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Hogaboam, C.M. et al.

Hogaboam, Bone-Larson, Steinhauser, Lukacs, Colletti, Simpson, Strieter, Kunkel,

Novel CXCR2-dependent liver regenerative qualities of ELR-containing CXC chemokines.

Severe acute liver injury due to accidental or intentional acetaminophen overdose presents a major clinical dilemma often requiring liver transplantation. In the present study, liver regeneration after profound liver injury in mice challenged with acetaminophen was facilitated by the exogenous addition of ELR-containing CXC chemokines such as macrophage inflammatory protein-2 (MIP-2), epithelial neutrophil-activating protein-78 (ENA-78), or interleukin 8. Intravenous administration of ELR-CXC chemokines or N-acetyl-cysteine (NAC) immediately after acetaminophen challenge in mice significantly reduced histological and biochemical markers of hepatic injury. However, when the intervention was delayed until 10 h after acetaminophen challenge, only ELR-CXC chemokines significantly reduced liver injury and mouse mortality. The delayed addition of ELR-CXC chemokines to cultured hepatocytes maintained the proliferation of these cells in a CXCR2-dependent fashion after acetaminophen challenge whereas delayed NAC treatment did not. These observations demonstrate that ELR-CXC chemokines represent novel hepatic regenerative factors that exhibit prolonged therapeutic effects after acetaminophen-induced hepatotoxicity.[1]

References

Novel CXCR2-dependent liver regenerative qualities of ELR-containing CXC chemokines. Hogaboam, C.M., Bone-Larson, C.L., Steinhauser, M.L., Lukacs, N.W., Colletti, L.M., Simpson, K.J., Strieter, R.M., Kunkel, S.L. FASEB J. (1999) [Pubmed]

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