Pathways for clearance of surfactant protein A from the lung

Am J Physiol Lung Cell Mol Physiol. 2005 Dec;289(6):L1011-8. doi: 10.1152/ajplung.00250.2005. Epub 2005 Jul 8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / antagonists & inhibitors
  • Actins / metabolism
  • Amantadine / pharmacology
  • Animals
  • Arsenicals / pharmacology
  • Cells, Cultured
  • Clathrin / antagonists & inhibitors
  • Clathrin / metabolism
  • Cytochalasin D / pharmacology
  • Dopamine Agents / pharmacology
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Enzyme Inhibitors / pharmacology
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / metabolism
  • Male
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / metabolism*
  • Pulmonary Surfactant-Associated Protein A / metabolism*
  • Pulmonary Surfactant-Associated Protein A / pharmacology
  • Pulmonary Surfactants / metabolism*
  • Pulmonary Surfactants / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Actins
  • Arsenicals
  • Clathrin
  • Dopamine Agents
  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactants
  • oxophenylarsine
  • Cytochalasin D
  • Amantadine