COMPARATIVE IN-VIVO AND IN-VITRO MODELS TO APPROACH THE CELLULAR BASIS OF ENDOTOXIC-SHOCK - THE ROLE OF SINUSOIDAL LIVER-CELLS

During endotoxic shock, the liver exerts a lipopolysaccharide (LPS) cl earance function with the participation of both parenchymal and sinuso idal cells. Liver damage could be caused by LPS direct action, hypoxia and/or inflammatory mediators released by Kupffer cells. The aim of t his study is to establish an experimental model that could allow us to understand the direct E. coil 0111:B4 LPS action on sinusoidal cells. A comparative study was carried out, in vivo and in vitro, using eith er a rat reversible endotoxic shock model or sinusoidal cell cultures. The LPS was found to induce important and similar morphological alter ations both in vivo and in vitro, specially in Kupffer cells. These ce lls present mitochondrial damage, nuclear membrane swelling, and incre ased number of phagosomes, including lamellar bodies. An immunocolloid al gold technique shows, in vitro, the LPS mainly located on Kupffer c ell membrane and in phagosomes. The LPS binding to membrane, as a prim ary step of Kupffer cell activation, increases the phagocytosis. This effect could be related to a decrease of fluidity on the external memb rane portion.