Autoradiographic determination of permeation pathway of permeability probes across intestinal and tracheal epithelia.
Mucosal permeability studies are used to assess intestinal and respiratory barrier functions. Our ability to interpret results of permeability studies are hampered by our lack of understanding of absorptive pathways of permeability markers. The aim of this study was to visually trace the pathway of permeability probes across the small intestinal and tracheal epithelia by using electron microscopic autoradiography and cytochemistry. We saw a constant rate of mucosal to serosal permeation of intestinal permeability probes polyethylene glycol 400 (PEG-400) and mannitol across the everted small intestinal sac and of the pulmonary permeability probe bovine serum albumin (BSA) across the tracheal epithelia. Electron microscopic tracing of the permeation pathways of tritiated PEG-400 and tritiated mannitol revealed that the majority of the probes traversed the intestinal epithelium paracellularly within 1 half distance (1650 A) of the intercellular space. It is interesting that we also found a small but significant transcellular transport of permeability probes. Goblet cells also absorbed permeability probes transcellularly, but in an "all or none" fashion. Similar pathways were identified in studies utilizing the commonly used pulmonary permeability probes iodine 125-labeled BSA and horseradish peroxidase to determine the routes of transfer in the airway epithelia. In the normal unperturbed trachea, these large permeability probes traversed the pulmonary epithelia transcellularly via endocytosis. On barrier disruption by cytochalasin D, the probes permeated predominantly via the paracellular pathway. This study also demonstrates some of the similarities and differences in transmucosal pathways shared by intestinal and pulmonary epithelia.
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Department of Medicine, Department of Veterans Administration Medical Center at Long Beach, CA.
Hollander
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Riga
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Bhalla
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D000818:Animals; D001345:Autoradiography; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D015638:Cytochalasin D / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology / Q000648:ultrastructure; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D007422:Intestines / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D007457:Iodine Radioisotopes; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics*; D051379:Mice; D008854:Microscopy, Electron; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*; D014132:Trachea / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure
D007457:Iodine Radioisotopes; D015638:Cytochalasin D; D012710:Serum Albumin, Bovine; D008353:Mannitol; D011092:Polyethylene Glycols; D006735:Horseradish Peroxidase