The selective hepatic uptake of desialylated peripheral blood mononuclear cells in rabbits

Abstract

The effect of desialylation (i.e., neuraminidase treatment) of peripheral blood mononuclear cells on their clearance from the circulation has been studied in rabbits. When autologous 51Cr-labeled normal and desialylated peripheral blood mononuclear cells were administered intravenously to rabbits 21.9 ± 3.3% (standard deviation) and 37.7 ± 9.2% of the injected radioactivity was recovered from the liver at 1 hr, respectively (P < 0.001). In analogous experiments using purified preparations of normal and desialylated peripheral blood lymphocytes, the mean recovery of injected radioactivity from the liver was 14.3% and 25.4%, respectively. Although it was not proved morphologically that preferential hepatic uptake of radioactivity reflected the uptake of labeled viable cells, these findings are compatible with a preferential hepatic uptake of desialylated peripheral blood mononuclear cells and, more specifically, of desialylated peripheral blood lymphocytes in this species. When labeled desialylated peripheral blood mononuclear cells were infused after rabbits had been depleted of complement, the radioactivity recovered from the liver at 1 hr (36.6 ± 9.8%) was similar to that in corresponding experiments in the presence of complement, which suggests that the preferential hepatic uptake of desialylated peripheral blood mononuclear cells is independent of the complement system. In contrast, when labeled desialylated peripheral blood mononuclear cells, which had been preincubated with nonimmune rabbit immunoglobulin G Fab fragments, were infused, radioactivity recovered from the liver at 1 hr (23.6 ± 4.0%) was similar to that after infusing labeled normal peripheral blood mononuclear cells. Preincubation with Fab fragments did not diminish the hepatic uptake of radioactivity after infusing labeled normal peripheral blood mononuclear cells. These observations can be explained by postulating that the preferential hepatic uptake of desialylated peripheral blood mononuclear cells is mediated by cell bound antibody. Inhibition of this process by preincubation with Fab fragments would occur if Fab binding to antigens, which are exposed on the surface of peripheral blood mononuclear cells by desialylation, results in blocking of the binding of naturally occurring circulating antibodies to these antigens. It is suggested that desialylated peripheral blood mono-nuclear cells become coated with naturally occurring antibodies in vivo with the result that subsequent recognition of cell-bound antibody by Fc receptors on Kupffer cells mediates their selective hepatic uptake.