Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting

doi:10.1084/jem.184.3.1045

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Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting

A Frey, KT Giannasca, R Weltzin, PJ Giannasca, H Reggio, WI Lencer and MR Neutra
Department of Pediatrics, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115, USA.

Transepithelial transport of antigens and pathogens across the epithelial barrier by M cells may be a prerequisite for induction of mucosal immunity in the intestine. Efficient transport of antigens and pathogens requires adherence to M cell apical surfaces. Coupling of antigen-containing particles to the pentameric binding subunit of cholera toxin (CTB) has been proposed as a means for increasing antigen uptake because the CTB receptor, ganglioside GM1, is a glycolipid present in apical membranes of all intestinal epithelial cells. To test the accessibility of enterocyte and M cell membrane glycolipids to ligands in the size ranges of viruses, bacteria, and particulate mucosal vaccines, we analyzed binding of CTB probes of different sizes to rabbit Peyer's patch epithelium. Soluble CTB-fluorescein isothiocyanate (diameter 6.4 nm) bound to apical membranes of all epithelial cells. CTB coupled to 14 nm colloidal gold (final diameter, 28.8 nm) failed to adhere to enterocytes but did adhere to M cells. CTB- coated, fluorescent microparticles (final diameter, 1.13 microns) failed to adhere to enterocytes or M cells in vivo or to well- differentiated Caco-2 intestinal epithelial cells in vitro. However, these particles bound specifically to GM1 on BALB/c 3T3 fibroblasts in vitro and to undifferentiated Caco-2 cells that lacked brush borders and glycocalyx. Measurements of glycocalyx thickness by electron microscopy suggested that a relatively thin (20 nm) glycocalyx was sufficient to prevent access of 1-micron microparticles to glycolipid receptors. Thus, the barrier function of the intestinal epithelial cell glycocalyx may be important in limiting microbial adherence to membrane glycolipids, and in CTB-mediated targeting of vaccines to M cells and the mucosal immune system.
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Harokopakis, E., Hajishengallis, G., Michalek, S. M. (1998). Effectiveness of Liposomes Possessing Surface-Linked Recombinant B Subunit of Cholera Toxin as an Oral Antigen Delivery System. Infect. Immun. 66: 4299-4304 [Abstract] [Full Text]
Beier, R., Gebert, A. (1998). Kinetics of particle uptake in the domes of Peyer's patches. Am. J. Physiol. Gastrointest. Liver Physiol. 275: G130-G137 [Abstract] [Full Text]
Neutra, M. R. (1998). V. Role of M cells in transepithelial transport of antigens and pathogens to the mucosal immune system. Am. J. Physiol. Gastrointest. Liver Physiol. 274: G785-G791 [Abstract] [Full Text]
Hicks, S., Frankel, G., Kaper, J. B., Dougan, G., Phillips, A. D. (1998). Role of Intimin and Bundle-Forming Pili in Enteropathogenic Escherichia coli Adhesion to Pediatric Intestinal Tissue In Vitro. Infect. Immun. 66: 1570-1578 [Abstract] [Full Text]
Poulain-Godefroy, O., Mielcarek, N., Ivanoff, N., Remoue, F., Schacht, A.-M., Phillips, N., Locht, C., Capron, A., Riveau, G. (1998). Bordetella pertussis Filamentous Hemagglutinin Enhances the Immunogenicity of Liposome-Delivered Antigen Administered Intranasally. Infect. Immun. 66: 1764-1767 [Abstract] [Full Text]