Bidirectional transcytosis of IgG by the rat neonatal Fc receptor expressed in a rat kidney cell line: a system to study protein transport across epithelia

The neonatal Fc receptor, FcRn, transports immunoglobulin G (IgG) across ce llular barriers between mother and offspring. FcRn also protects circulatin g IgG from catabolism, probably during transport across the capillary endot helium, Only one cell culture model of transcytosis has been used extensive ly, the transport of IgA from the basolateral to the apical surface of Madi n-Darby canine kidney cells by the polymeric immunoglobulin receptor (pIgR) , We report that rat inner medullary collecting duct (IMCD) cells transfect ed with DNA encoding the a subunit of rat FcRn specifically and saturably t ransport Fc when grown as polarized monolayers, Using this system, we have found that transcytosis by FcRn, like transcytosis by the pIgR, depends upo n an intact microtubule system. FcRn differs most strikingly from the pIgR in its ability to transport its ligand in both the apical to basolateral an d basolateral to apical directions, The phosphatidylinositol 3-kinase inhib itors wortmannin and LY294002 inhibited basolateral to apical transport by FcRn more than apical to basolateral transport, suggesting that there are d ifferences in the mechanisms of transport in the two directions. Lastly, we found that transcytosis by FcRn depends upon vesicular acidification. We a nticipate that the IMCD cell culture model will allow further elucidation o f the mechanism of IgG transport by FcRn.