Burn injury sensitizes rat Kupffer cells via mechanisms dependent on gut-derived endotoxin

Enomoto, Nobuyuki; Takei, Yoshiyuki; Yamashina, Shunhei; Fukuda, Toru; Suzuki, Satoko; Ikejima, Kenichi; Kitamura, Tsuneo; Sato, Nobuhiro
December 2004
Journal of Gastroenterology;2004, Vol. 39 Issue 12, p1175
Academic Journal
Background. Bacterial translocation occurs after thermal injury in association with intestinal harrier loss. Recently, we found that sensitization of Kupffer cells involved gut-derived endotoxin; therefore, the purpose of this work was to study the mechanisms of sensitization of Kupffer cells in hum injury. Methods. Rats received a 30% body surface area full-thickness steam hum 24h before experiments. Serum alanine aminotransferase (ALT) was measured to assess liver damage, and plasma endotoxin in the portal vein were measured. Kupffer cells were isolated 24h after the burn. Intracellular calcium ([Ca2+]) in Kupffer cells was measured using a microspectrofluorometer with the fluorescent indicator, fura-2, and tumor necrosis factor (TNF)-α was measured by enzyme-linked immunosorbent assay (ELISA). Results. Lipopolysaccharide (LPS)-induced mortality was increased by burn treatment. This increase was blocked by gadolinium chloride, a Kupffer-cell toxicant. Accordingly, Kupffer cells were involved in this system. The LPS-induced increase of ALT was upregulated by the burn injury. This increase was blocked by pretreatment with antibiotics. Endotoxin levels were increased to almost 300pg/ml (normal, <20pg/ml) in the portal veins of rats that received a burn. This increase was blunted by antibiotics. In Kupffer cells isolated from untreated control rats, [Ca2+] increased to 82 ± 7nM after the addition of LPS (100 ng/ml). Levels were elevated twofold over control levels in the cells from rats with hum (174 ± 15 nM). In addition, TNF-α production by Kupffer cells isolated from rats with burn was increased fourfold over the based level. Sterilization of the gut with antibiotics completely blocked all effects of the hum on [Ca2+], and TNF-α release. Conclusions. Kupffer cells isolated from rats with hum exhibited sensitization to LPS, involving gut-derived endotoxin. It is concluded that burns sensitize Kupffer cells to LPS via mechanisms that are dependent on gut-derived endotoxin.


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