GEORGE LÄZÄR, ELIZABETH HUSZTIK and GEORGE LÄZÄR, JR.1
Institute of Pathophysiology, 'Department of Surgery, University of Szeged, Szeged, Hungary ABSTRACT
In the nineteenth century, it was realized that certain cells were intensely phagocytic. These varied cell types which acted in host defence by phagocytosing of foreign invaders such as microbes were grouped collectively into the reticuloendothelial system (RES). In studies of the physiological and pathophysiological roles of the RES, depression or blockade of the granulopetic activity of this system has attracted considerable attention. Authors describe their experiments demonstrating that rare earth metal salts, among them gadolinium chloride (GdCl3), depress the reticuloendothelial activity, selectively depressing or eliminating the large Kupffer cells. Recent studies from many laboratories have shown that the Kupffer cell blockade induced by GdCl3 modifies the immune response, exerts protective effects on anaphylactic and endotoxic/septic shock, and decreases the liver-damaging effects of several hepatotoxins and ischaemic reperfusion. Recent studies have elucidated the mechanisms by which GdCl3-induced Kupffer cell blockade protects against a variety of hepatotoxic processes. GdCl is most likely protective because it prevents the release of inflammatory cytokines and toxic oxygen radicals produced by activated Kupffer cells. The causal roles of these mechanisms have been shown to be important in the prevention of hepatotoxic injuries caused by hepatotoxins, such as carbon tetrachloride and alcohol, or liver injuries associated with ischaemia-reperfusion, liver transplantation and sepsis.
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