Role of F4/80+Mac-1high adherent non-parenchymal liver cells in concanavalin A-induced hepatic injury in mice

Authors


Dr Ayako Mabuchi, Microcirculation Research Laboratory, Department of Physiology, Otago School of Medical Science, University of Otago, Dunedin 9054, New Zealand. Email: ayako.mabuchi@stonebow.otago.ac.nz

Abstract

Aim:  Non-parenchymal liver cells (NPLC) play an important role in the regulation of immune responses and the inflammatory process. In this study, we hypothesized that F4/80+Mac-1high+ cells were involved in the regulative feedback-modulated regulation of inflammatory responses during concanavalin A (Con A)-induced hepatitis.

Methods:  Hepatitis was induced in BALB/c mice by the intravenous injection of Con A. Liver injury was assessed using serum aminotransferase and pathology. The function of NPLC was assessed by FACS analysis. Accessory cell function of adherent Con A NPLC was performed with an ovalbumin specific T-helper 1 (Th1) clone proliferation assay. The culture supernatant nitric oxide (NO) content was quantified by the Griess reaction. Inducible NO synthase (iNOS) expression was demonstrated by immunohistochemistry and Western blot analysis.

Results:  The number of hepatic F4/80+Mac-1high+cells increased in a time-dependent manner after Con A administration, which consequently suppressed Th1 cell proliferation by a mechanism likely to involve NO. The iNOS expression of NPLC was elevated at 24 h post-Con A injection. In nude mice, F4/80+Mac-1high+cells did not increase in the Con A-treated liver; the NPLC did not suppress Th1 clone proliferation.

Conclusion:  These findings suggest that the in vivo activation of F4/80+Mac-1high+cells by Con A administration suppresses Th1 cell proliferation by increasing NO, and subsequently reducing liver injury.

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