STIMULATED KUPFFER CELLS ATTRACT CYTOTOXIC T-LYMPHOCYTES (CTL) AND INCREASE THE ADHESION OF CTL TO SINUSOIDAL ENDOTHELIAL-CELLS

Kupffer cells secrete many kinds of cytokines, and Kupffer cell-derive d substances regulate the recruitment of neutrophils and monocytes in the liver. To investigate the roles of Kupffer cells in the extravasat ion of cytotoxic T lymphocytes (CTL), we examined whether supernatants of lipopolysaccharide (LPs)-stimulated rat Kupffer cells have chemota ctic activity for CTL and enhance adhesion of CTL to sinusoidal endoth elial cells. The study using a modified Boyden's chamber demonstrated that the supernatants of LPS-stimulated Kupffer cells were chemoattrac tant for CTL and the concentration-response curve was bell shaped whic h is typical in in vitro chemotaxis assays. In addition, incubating CT L with the supernatants of LPS-stimulated Kupffer cells enhanced the a dhesion of CTL to monolayers of sinusoidal endothelial cells to 2.3 ti mes higher than controls in a 60-min assay. Anti-lymphocyte function-a ssociated antigen-1 alpha (LFA-1 alpha) antibody blocked the increased adhesion of CTL by LPS-stimulated Kupffer cells. These results indica ted that Kupffer cells play important roles in infiltration of CTL reg ulated by LFA-1 alpha-associated bindings in the hepatic