Human Pulmonary Surfactant Protein SP-A1 Provides Maximal Efficiency of Lung Interfacial Films

Abstract

Pulmonary surfactant is a lipoprotein complex that reduces surface tension to prevent alveolar collapse and contributes to the protection of the respiratory surface from the entry of pathogens. Surfactant protein A (SP-A) is a hydrophilic glycoprotein of the collectin family, and its main function is related to host defense. However, previous studies have shown that SP-A also aids in the formation and biophysical properties of pulmonary surfactant films at the air-water interface. Humans, unlike rodents, have two genes, SFTPA1 and SFTPA2. The encoded proteins, SP-A1 and SP-A2, differ quantitatively or qualitatively in function. It has been shown that both gene products are necessary for tubular myelin formation, an extracellular structural form of lung surfactant. The goal of this study was to investigate potential differences in the biophysical properties of surfactants containing human SP-A1, SP-A2, or both. For this purpose, we have studied for the first time, to our knowledge, the biophysical properties of pulmonary surfactant from individual humanized transgenic mice expressing human SP-A1, SP-A2, or both SP-A1 and SP-A2, in the captive bubble surfactometer. We observed that pulmonary surfactant containing SP-A1 reaches lower surface tension after postexpansion interfacial adsorption than surfactants containing no SP-A or only SP-A2. Under interfacial compression-expansion cycling conditions, surfactant films containing SP-A1 also performed better, particularly with respect to the reorganization of the films that takes place during compression. On the other hand, addition of recombinant SP-A1 to a surfactant preparation reconstituted from the hydrophobic fraction of a porcine surfactant made it more resistant to inhibition by serum than the addition of equivalent amounts of SP-A2. We conclude that the presence of SP-A1 allows pulmonary surfactant to adopt a particularly favorable structure with optimal biophysical properties.

In Vitro Functional and Structural Characterization of A Synthetic Clinical Pulmonary Surfactant with Enhanced Resistance to Inhibition

“…However, for optimal interfacial adsorption of surfactant, not only the two hydrophobic proteins, SP-B and SP-C, but also the collectin SP-A play a key role. The latter seems very important to maintain a packed reservoir interconnected to the interface, thus contributing to the re-adsorption and expansion of new material during each compression cycle 19 . The presence of SP-A explains the best rates of both adsorption and accumulation at the interface of NS, compared with the SP-A-free clinical materials.…”

Impact of Surfactant Protein-A Variants on Survival in Aged Mice in Response to Klebsiella pneumoniae Infection and Ozone: Serendipity in Action

“…Furthermore, the SP-A variant-dependent AM gene expression in response to infection varies in a sex-specific manner [ 60 ]. SP-A1 compared to SP-A2 exhibits a higher efficiency in pulmonary surfactant reorganization and surfactant inhibition by serum proteins [ 61 ], whereas SP-A2 exhibits higher activity in host defense-related functions [ 35 , 39 , 45 ]. The major contributor for at least some of these differences appears to be amino acid 85 of the precursor molecule, where SP-A1 has a cysteine and SP-A2 has an arginine [ 31 , 42 ].…”

Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis

“…Pulmonary surfactant is synthesized and secreted by the alveolar epithelial Type II cells of the lung and maintains the stability of the pulmonary tissue by reducing the surface tension of fluids that coat the lung. Broadly speaking the hydrophobic surfactant proteins (SP-B and SP-C) are primarily involved in surface properties of surfactant and are important for normal lung function ( 7 ); the hydrophilic proteins (SP-A1, SP-A2, and SP-D) are primarily involved in host defense ( 6 , 8 , 9 ), although SP-A1 and SP-A2 exhibit differential effects on the surfactant structural reorganization ( 10 ), on the organization of phospholipid monolayers containing SP-B ( 11 ), and lung mechanics ( 12 ). Moreover, lipid-mediated interactions of SP-A/SP-B may contribute to normal lung surfactant function ( 13 ).…”

“…This indicates that the structural organization of SP-A affects its functional activity and this is linked to disease severity ( 32 ). SP-A1, shown previously to form higher size oligomers compared to SP-A2 ( 33 ), was shown recently to affect more efficiently (than SP-A2) the structural organization of surfactant, which in turn may affect lung function ( 10 ). Furthermore, genetic associations of SFTPA1 and SFTPA2 with CF have been observed ( 34 ).…”