title: Effect of endocytosis inhibitors on alveolar clearance of albumin, immunoglobulin G, and SP-A in rabbits.
abstract: Protein in the alveolar space may be cleared by endocytosis and degradation inside alveolar epithelial cells, by transcytosis across the alveolar epithelium, or by restricted diffusion through the epithelium. The relative contributions of these three pathways to clearance of large quantities of protein from the air spaces is not known. This study investigated the effects of monensin and nocodazole, agents which inhibit endocytosis in cell culture, on alveolar epithelial protein transport in anesthetized rabbits. There was evidence that monensin and nocodazole inhibited endocytosis by the alveolar epithelium in vivo. Nocodazole increased the number of vesicles in the alveolar epithelium and capillary endothelium. Monensin increased vesicle density in the endothelium. These results suggested that the inhibitors disrupted microtubules or interrupted cellular membrane traffic in the lung. Both inhibitors decreased lung parenchymal uptake of immunoreactive human albumin from the air spaces. Monensin and nocodazole inhibited albumin uptake in cultured alveolar type II cells. Monensin increased the amount of 125I-labeled surfactant protein A associated with the lungs, compared with the quantity remaining in the air space 2 h after instillation. Although the drugs decreased alveolar epithelial protein uptake, they did not decrease alveolar clearance of 125I-labeled immunoglobulin G or 131I-labeled albumin in anesthetized rabbits. Thus monensin- and nocodazole-sensitive protein-uptake pathways do not account for most alveolar protein clearance when the distal air spaces are filled with a protein solution.
authors.affiliation: Department of Anesthesia, San Francisco General Hospital, California.
authors.forename: R H
authors.initials: RH
authors.lastname: Hastings
authors.forename: J R
authors.initials: JR
authors.lastname: Wright
authors.forename: K H
authors.initials: KH
authors.lastname: Albertine
authors.forename: R
authors.initials: R
authors.lastname: Ciriales
authors.forename: M A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D008168:Lung / Q000502:physiology*; D008657:Metabolic Clearance Rate; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology*; D015739:Nocodazole / Q000494:pharmacology*; D011510:Proteolipids / Q000493:pharmacokinetics*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000493:pharmacokinetics*; D011817:Rabbits; D012709:Serum Albumin / Q000493:pharmacokinetics*
chemical_list: D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012709:Serum Albumin; D008985:Monensin; D016650:Fluorescein-5-isothiocyanate; D015739:Nocodazole