Fc Gamma Receptors in the Hepatic Sinusoid

Introduction Receptors that recognize the Fc-portion of antibodies mediate endocytosis of antibody-containing complexes (ICs) [1,2]. The liver is the main organ for uptake of IC from circulation. Phagocytosis of antibody-coated particles takes place in Kupffer cells (KC) whereas endocytosis of soluble IC takes place both in KC and in liver endothelial cells (LEC) [3,4]. ICs have, in comparison with ligands of the mannose-receptor or the scavenger receptors, been shown to be delayed in the endocytic pathway en route to lysosomes [4,5] suggesting that the ICs and the Fc gamma Rs may use a unique pathway to lysosomes. Whereas the receptors of mannose and scavenger receptors are recycled constitutively between endosomes and plasma membrane, with or without bound ligand [6], the traffic of the Fc gamma R may be controlled by the ligand. Polyvalent ligands (ICs) which bring about receptor cross-linking may direct the receptor-ligand-complex from a recycling route to late endosomes and eventually to lysosomes. The latter pathway will lead to receptor-downregulation [7]. Few studies have been done to determine whether hepatic Fc gamma Rs are subject to downregulation by their specific ligands. If these receptors were lost from KC and/or LEC after uptake of immune complexes a fatal result would be that the liver were left defenseless until new receptors were synthesized. The purpose of the present investigation was to determine whether uptake of polyvalent ligands would bring about a reduction in the number of Fc gamma Rs in rat KC and LEC.