EFFECT OF KUPFFER CELL PHAGOCYTOSIS BLOCKADE INDUCED BY GADOLINIUM CHLORIDE AND CARRAGEENAN ON ENDOTOXIN SENSITIVITY, TISSUE LOCALIZATION OF ENDOTOXIN AND TNF PRODUCTION

Several recent data suggest that in severe injuries, such as a shock s tate, the gradual activation of Kupffer cells and the excessive releas e of destructive and immunosuppressive products from macrophages may c ontribute to the development of ''multiple organ failure''. The effect of Kupffer cell phagocytosis blockade on the correlation between the tissue distribution of bacterial lipopolysaccharide (LPS), endotoxin s ensitivity and LPS-induced tumor necrosis factor (TNF) production was investigated in in vivo experiments in mice. To depress the activity o f the Kupffer cells, gadolinium chloride (GdCl3) or carrageenan was us ed. The studies indicated the dissociation of the tissue localization of Cr-51-labeled endotoxin and endotoxin lethalithy. Both GdCl3 and ca rrageenan depressed the Kupffer cell activity, but the endotoxin sensi tivity was enhanced only by carrageenan treatment. However, there was a close correlation between the sensitivity to LPS and LPS-induced TNF production as measured in the serum, since LPS-induced TNF production was enhanced only by carrageenan treatment.