Pathways for clearance of surfactant protein A from the lung.
Uptake and degradation of (125)I-surfactant protein A (SP-A) over a 1-h period was studied in alveolar cells in culture and in isolated perfused lungs to elucidate the mechanism for clearance of the protein from the alveolar space. Specific inhibitors of clathrin- and actin-dependent endocytosis were utilized. In type II cells, uptake of SP-A, compared with controls, was decreased by 60% on incubation with clathrin inhibitors (amantadine and phenylarsine oxide) or with the actin inhibitor cytochalasin D. All agents reduced SP-A metabolism by alveolar macrophages. Untreated rat isolated perfused lungs internalized 36% of instilled SP-A, and 56% of the incorporated SP-A was degraded. Inhibitors of clathrin and actin significantly reduced SP-A uptake by approximately 54%, whereas cytochalasin D inhibited SP-A degradation. Coincubation of agents did not produce an additive effect on uptake of SP-A by cultured pneumocytes or isolated perfused lungs, indicating that all agents affected the same pathway. Thus SP-A clears the lung via a clathrin-mediated pathway that requires the polymerization of actin.
Jain
Deepika
D
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, 1 John Morgan Bldg., 3620 Hamilton Walk, Philadelphia, PA 19104-6068, USA.
Dodia
Chandra
C
Fisher
Aron B
AB
Bates
Sandra R
SR
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002478:Cells, Cultured; D002966:Clathrin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism* / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D001152:Arsenicals; D002966:Clathrin; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D037662:Pulmonary Surfactant-Associated Protein A; D011663:Pulmonary Surfactants; C029341:oxophenylarsine; D015638:Cytochalasin D; D000547:Amantadine