Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0405179 on January 13, 2006

Published online before print January 13, 2006
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(Journal of Leukocyte Biology. 2006;79:809-817.)
© 2006 by Society for Leukocyte Biology

The Kupffer cell protects against acute lung injury in a rat peritonitis model: role of IL-10

Hiroshi Kono*,1, Hideki Fujii*, Yu Hirai*, Masato Tsuchiya*, Hidetake Amemiya*, Masami Asakawa*, Akira Maki*, Masanori Matsuda* and Masayuki Yamamoto{dagger}

* First Department of Surgery, University of Yamanashi, Japan; and
{dagger} Department of Surgery, Shinko Byoin Hospital, Hyogo, Japan

1Correspondence: First Department of Surgery, University of Yamanashi, 1110 Shimokato, Tamaho, Nakakoma, Yamanashi 409-3898, Japan. E-mail: hkouno{at}res.yamanashi-med.ac.jp

The possibility that Kupffer cells (KCs) play key beneficial and deleterious roles in multiple organ injury in sepsis has been discussed. The role of KCs in lung injury in a rat peritonitis model was investigated. Specifically, the involvement of interleukin (IL)-10, which has anti-inflammatory effects, was examined. Rats were given saline or gadolinium chloride (GdCl3), a KC toxicant, 24 h before cecal ligation and puncture (CLP). Survival was assessed for 7 days after CLP. The liver, lung, and serum were harvested, and the expression of cytokines was assessed. Macrophages were isolated from each organ after CLP, and the mRNA expression of inflammatory mediators was assessed. GdCl3 treatment increased lung injury and mortality. Plasma endotoxin levels were significantly greater, whereas serum IL-10 levels were lower in the GdCl3 than in the control group after CLP. IL-10 levels were significantly greater in the aorta than the hepatic vein. The mRNA expression of IL-10 was less in KCs from the GdCl3 than the control group. In the liver, the expression of IL-10 increased rapidly and continuously, up to 9 h in the control group, but values were significantly lower in the GdCl3 group. Rabbit anti-rat IL-10 antibodies were injected just after CLP to investigate the effects of immunoneutralization of endogenously produced IL-10. In the antibody-treated group, lung injury and mortality increased compared with animals treated with rabbit immunoglobulin G. Taken together, these results indicate that KCs play a protective role in lung injury in sepsis by production of IL-10.

Key Words: acute respiratory distress syndrome • inflammatory cytokine • lung macrophage and endotoxemia




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