Role of F4/80Mac-1 adherent non-parenchymal liver cells in concanavalin A-induced hepatic injury in mice.
OBJECTIVE
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-1(high+) 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-1(high+)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-1(high+)cells did not increase in the Con A-treated liver; the NPLC did not suppress Th1 clone proliferation.


CONCLUSIONS
These findings suggest that the in vivo activation of F4/80(+)Mac-1(high+)cells by Con A administration suppresses Th1 cell proliferation by increasing NO, and subsequently reducing liver injury.
Mabuchi
Ayako
A
Department of Physiology, Otago University, Dunedin, New Zealand; and Department of Microbiology and Immunology, Nippon Medical School, Japan.
Nagao
Tomokazu
T
Koshio
Osamu
O
Ishiwata
Toshiyuki
T
Yano
Akihiko
A
Suzuki
Kazuo
K
Yokomuro
Kozo
K
Wheatley
Antony M
AM