Intestinal Uptake of Macromolecules (original) (raw)
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The Uptake of Soluble and Particulate Antigens by Epithelial Cells in the Mouse Small Intestine
PLoS ONE, 2014
Intestinal epithelial cells (IECs) overlying the villi play a prominent role in absorption of digested nutrients and establish a barrier that separates the internal milieu from potentially harmful microbial antigens. Several mechanisms by which antigens of dietary and microbial origin enter the body have been identified; however whether IECs play a role in antigen uptake is not known. Using in vivo imaging of the mouse small intestine, we investigated whether epithelial cells (enterocytes) play an active role in the uptake (sampling) of lumen antigens. We found that small molecular weight antigens such as chicken ovalbumin, dextran, and bacterial LPS enter the lamina propria, the loose connective tissue which lies beneath the epithelium via goblet cell associated passageways. However, epithelial cells overlying the villi can internalize particulate antigens such as bacterial cell debris and inert nanoparticles (NPs), which are then found co-localizing with the CD11c+ dendritic cells in the lamina propria. The extent of NP uptake by IECs depends on their size: 20-40 nm NPs are taken up readily, while NPs larger than 100 nm are taken up mainly by the epithelial cells overlying Peyer's patches. Blocking NPs with small proteins or conjugating them with ovalbumin does not inhibit their uptake. However, the uptake of 40 nm NPs can be inhibited when they are administered with an endocytosis inhibitor (chlorpromazine). Delineating the mechanisms of antigen uptake in the gut is essential for understanding how tolerance and immunity to lumen antigens are generated, and for the development of mucosal vaccines and therapies.
Factors affecting antigen uptake by human intestinal epithelial cell lines
Digestive diseases and sciences, 2000
We assessed the role of size, solubility, and prophagocytic cytokines interferon-gamma (IFN-gamma), and granulocyte-macrophage colony stimulatory factor (GM-CSF) in antigen uptake and kinetics by intestinal epithelial cells using keyhole limpet hemocyanin and ovalbumin. Both fluoresceinated keyhole limpet hemocyanin (3000-7500 kDa) and fluoresceinated ovalbumin (45 kDa) were internalized by human colonic epithelial cell lines, with kinetics similar to those of fluoresceinated tetanus toxoid, and there was decreased uptake of insoluble immune complexes and no enhancement in the uptake of soluble immune complexes. In addition, neither IFN-gamma nor GM-CSF altered the kinetics of uptake nor enhanced antigen internalization by the intestinal epithelial cell lines. These data suggest that regardless of the size of the soluble antigen, the presence of prophagocytic cytokines, or the formation of soluble immune complexes, fluid phase endocytosis of antigen by intestinal epithelial cells ap...
Gastrointestinal uptake and blood clearance of antigen in the presence of IgA antibodies
Immunology, 1983
In selected experiments, IgA antibodies with specificity for dinitrophenyl (DNP) groups appeared to prevent gastrointestinal passage of antigenic fragments of DNP-conjugated protein given orally to mice. The antigen did not, however, pass across the gut as an intact macromolecule even in control animals. IgA was not found to increase the blood clearance of DNP-conjugated protein given intravenously and it is concluded that IgA probably does not have any important role in mediating elimination of macromolecular antigens from the blood.
Hepatology, 1996
complement system also plays a crucial role in immune com-Immune complexes were formed between dinitropheplex (IC) handling. Thus, binding and activation of complenylated human serum albumin (DNP-HSA) and polyment increases IC solubility, reduces the risk of extrahepatic clonal rabbit immunoglobulin G (IgG) anti-DNP antiboddeposition, and mediates binding to complement-receptor ies at antibody excess. The antigen was labelled with bearing cells. [10][11][12][13][14] In primates, complement-containing ICs isotope ( 125 I-tyramine-cellobiose) or fluorochrome, (6bind to complement-receptor on erythrocytes, which deliver [fluorescein-5-(and-6)-carboxamido] hexanoic-acid, sucthe ICs to the reticuloendothelial system. 14,15 Complement cinimidyl ester). The radiolabelled antigen, native or deficiencies increase the risk of IC deposition outside of the antibody complexed, was given intravenously to rats.
Antigen uptake and trafficking in human intestinal epithelial cells
Digestive diseases and sciences, 2000
Primary intestinal epithelial cells, human colonic adenocarcinoma cell lines (DLD-1, Caco-2, and HT-29), and monocytes were used as model systems to study antigen uptake, antigen-presenting cell properties, as well as the kinetics of antigen uptake in intestinal epithelial cells (IEC). Intracellular staining of fluoresceinated tetanus toxoid was not evident in the IEC until after 30 min of incubation at 37 degrees C, whereas in monocytes intracellular punctate staining of fluoresceinated tetanus toxoid was evident after 5 mins. In polarized Caco-2 cells antigen could be internalized at both the apical and basolateral surfaces with polarized transport. When analyzed by electron microscopy, gold-labeled tetanus toxoid was internalized and found within endosomes and multivesicular bodies, but not within the lysosomal compartments by 60 min. By 2 hrs, gold-labeled tetanus toxoid was evident in the secondary lysosomes. These results demonstrate that tetanus toxoid follows an endocytic pa...
Secretory antibody response to local injection of soluble or particulate antigens in rats
Molecular Immunology, 1980
The locat antibody response to soluble (dinitrophenylated bovine gamma globulin: DNP-BGG) or particulate (DNP-~~re~~ffcoce~ mutans) antigens was examined in the rat. IgA and IgG antibody characteristics (concentration, activity and avidity) were determined in milk after injection of DNP-BGG or DNP-S. mutans into the vicinity of the mammary gland during gestation. More IgG antibody activity was detected in milk collected from rats injected with the soluble antigen relative to those injected with the particulate antigen using haptenated bacteriophage neutralization analysis. Analyses of milk antibody concentrations by combined immunoadsorption, elution and radial immunodiffusion confirmed the relative difference in response between the two antigens. IgA antibody levels in milk were similar in rats injected with soluble or particulate antigen (26 + 1 vs 27 + 7 pg/ml). However, the IgG antibody levels were higher in rats injected with the soluble antigen (24 f 2 vs 1 1 + 3 pg/ml). IgA antibody concentrations in saliva, determined by an enzyme linked immunosorbant assay, were also approximately the same after injection of soluble or particulate antigen (3 16 & 33 ng/ml vs 310 + 85 ng/ml) in the vicinity of the salivary glands. IgG antibody was only detected in the saliva of rats injected with soluble antigen (128 f 26 ng/ml). Therefore, differences in the local responses to the two antigens seemed to be confined to IgG antibody. Inhibition of bacteriophage neutralization by DNP-lysine and an analysis of neutralization kinetics revealed that IgA antibody may have a greater avidity for a multideterminant antigen than does IgG antibody in the same secretion.