The molecular configuration and ultrastructural locations of an IgG Fc binding site in human colonic epithelium.
Previously, we discovered a binding site for the Fc region of IgG in human small intestinal and colonic mucosa. The binding site (Fc gamma IBS) appeared to be primarily associated with goblet cells, to consist of greater than 200,000 Da and 78,000 Da components, and to be distinct from leukocyte FcR. In the present work, we used mAb made to colonocyte IgG-binding material to more accurately define the molecular structure and cellular locations of the Fc gamma IBS. In immunoblot and fast protein liquid chromatography analysis, the mAb revealed that the Fc gamma IBS consists of a 110,000- to 140,000-Da component in addition to the two components previously recognized. The greater than 200,000 component may be the critical component for IgG binding, inasmuch as mAb to it but not to the other two components inhibited binding of IgG to colonic sections in vitro. Used in immunoelectron microscopy, the mAb documented that the Fc gamma IBS is present in the endoplasmic reticulum of goblet cells, in the cytoplasmic matrix separating secretory granules of goblet cells, and within the granules themselves; occasionally it has the appearance of being secreted into the intestinal lumen with mucus. The Fc gamma IBS could not be solubilized from colonocyte homogenates by three different detergents, which suggests that it exists in complex with cytoskeletal elements. We speculate that the Fc gamma IBS aids in immunologic protection of the intestine by facilitating interaction between intestinal mucus and antigenic material in the lumen.
Kobayashi
K
K
Department of Medicine, Department of Veterans Affairs Medical Center, Denver, CO 80220.
Hamada
Y
Y
Blaser
M J
MJ
Brown
W R
WR
D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D015153:Blotting, Western; D003106:Colon / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008854:Microscopy, Electron; D008970:Molecular Weight; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism*; D012995:Solubility
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011961:Receptors, Fc