Abstract
Pulmonary surfactant is a complex mixture of lipids and proteins that is essential for postnatal function. Surfactant is synthesized in alveolar type II cells and stored as multi-bilayer membranes in a specialized secretory lysosome-related organelle (LRO), known as the lamellar body (LB), prior to secretion into the alveolar airspaces. Few LB proteins have been identified and the mechanisms regulating formation and trafficking of this organelle are poorly understood. Lamellar bodies were isolated from rat lungs, separated into limiting membrane and core populations, fractionated by SDS-PAGE and proteins identified by nanoLC-tandem mass spectrometry. In total 562 proteins were identified, significantly extending a previous study that identified 44 proteins in rat lung LB. The lung LB proteome reflects the dynamic interaction of this organelle with the biosynthetic, secretory and endocytic pathways of the type II epithelial cell. Comparison with other LRO proteomes indicated that 60% of LB proteins were detected in one or more of 8 other proteomes, confirming classification of the LB as a LRO. Remarkably the LB shared 37.8% of its proteins with the melanosome but only 9.9% with lamellar bodies from the skin. Of the 229 proteins not detected in other LRO proteomes, a subset of 34 proteins was enriched in lung relative to other tissues. Proteins with lipid-related functions comprised a significant proportion of the LB unique subset, consistent with the major function of this organelle in the organization, storage and secretion of surfactant lipid. The lung LB proteome will facilitate identification of molecular pathways involved in LB biogenesis, surfactant homeostasis and disease pathogenesis.
Highlights
The lung is composed of a tubular branching network that terminates in sac-like structures where gas-exchange occurs
Surfactant is a mixture of proteins (1–2% surfactant protein (SP)B and surfactant protein C (SP-C)) and lipids (80% phospholipids and,10% neutral lipids) that is synthesized by alveolar type II epithelial cells [5]
Antibodies directed against mature surfactant protein B (SP-B), SP-C, ABCA3, lysozyme and b actin were obtained from Seven Hills Bioreagents (Cincinnati, Ohio)
Summary
The lung is composed of a tubular branching network that terminates in sac-like structures (alveoli) where gas-exchange occurs. The air-blood barrier consists of thin type I epithelial cells that cover 95% of the alveolar surface [1], a basal lamina and the underlying capillary endothelium. Alveolar structure is critically dependent on the spreading of a phospholipid-rich film, pulmonary surfactant, at the air/liquid interface on the epithelial side of the air-blood barrier [2,3]. Surfactant insufficiency, due to premature birth, or inactivation, due to acute lung injury, results in increased surface tension and alveolar collapse leading to decreased gas exchange and respiratory distress syndrome [4]. Surfactant is a mixture of proteins (1–2% surfactant protein (SP)B and SP-C) and lipids (80% phospholipids and ,10% neutral lipids) that is synthesized by alveolar type II epithelial cells [5]. The LB plays an important role in integrating the surfactant biosynthetic and recycling pathways to maintain the intracellular surfactant pool
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