The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat

Abstract

The transport of immunoglobulins across the intestinal mucosa of neonatal rats provides an excellent model for the study of transcellular protein transport. The mechanism of intestinal uptake and transcellular transport of plasma proteins has been studied in 12-14-day old rats using intraduodenally administered radioiodinated proteins. Appreciable quantities of rat IgG, mouse IgG, rabbit IgG, and all four subclasses of human IgG were taken up by the intestinal wall (19-54% of administered dose at 4 hr) and transported to the animal (10-35% of administered dose at 4 hr). In contrast there was little or no uptake of human IgM, IgA, and IgE and little or no transport of human IgM, IgA, IgD, IgE, albumin, transferrin, and ceruloplasmin. Both the uptake and transport of labeled IgG were significantly inhibited by unlabeled IgG. Further insight into the transport process was obtained from the observation that an appreciable proportion of the label of IgG in intestinal wall homogenates, but not in plasma or intestinal washings, migrated in a sucrose ultracentrifugation gradient much more rapidly than did the administered 7S molecules. This pattern was not observed with other proteins studied. This apparent binding of labeled IgG was also markedly inhibited by unlabeled IgG. In subcellular fractionation studies of intestinal homogenates the complexed labeled IgG was shown to be associated predominantly with cell membrane rather than cell sap fractions. In addition IgG could be shown to bind to purified enterocyte microvillous membranes in vitro. It is concluded that in the neonatal rat: (a) the major processes involved in both intestinal uptake and transport of IgG are specific and saturable; (b) intestinal transport is associated with complexing of IgG molecules with membranes, most probably with enterocyte microvillous membranes; and (c) the part of the IgG structure involved in this process is probably similar to that involved in the concentration-catabolism effect but is not identical to that mediating other non-antigen combining functions of IgG. Our data are consistent with the existence of specific receptors for IgG on enterocyte microvillous membranes of the neonatal rat. Such receptors would be necessary for the specific uptake and transport of these molecules.