Human SP-A1 Enhances Interfacial Properties of Lung Surfactant and Restores a Proper Behavior in the Presence of Inhibitory Agents

Abstract

Pulmonary surfactant is a lipid-protein complex secreted by type II alveolar cells. This surface-active agent prevents alveolar collapse by reducing surface tension at the respiratory air-liquid interface during expiration and contributes to the innate defense of the lung. Surfactant protein A (SP-A) is a hydrophilic collectin protein implicated mainly in the host defense. However, it has been shown that SP-A participates in the formation of surfactant films at the interface and helps to reestablish the biophysical properties of surfactant when this is impaired by the presence of some inhibitors. There are two SP-A genes in humans, SFTPA1 and SFTPA2, which products differ in structure and function. With the aim of investigating the differences in the biophysical properties of surfactant containing human SP-A1, SP-A2 or both, we have studied 1) pulmonary surfactant from individual humanized transgenic mice expressing human SP-A1, SP-A2, or both SP-A1/2, in a Captive Bubble Surfactometer (CBS), and 2) the capability of this two variants of the protein to restore the biophysical activity of a reconstituted organic extract (OE) from native porcine surfactant in the presence of serum as inhibitory agent, mimicking a situation of lung injury. The experiments revealed consistent functional differences in surfactant containing SP-A1 or SP-A2. In the presence of serum, surfactant from mice containing SP-A1 and the OE reconstituted upon addition of SP-A1, achieved lower surface tension after post-expansion interfacial adsorption and a more efficient reorganization of the film under interfacial compression-expansion cycling conditions, than surfactants containing no SP-A or only SP-A2. We conclude that the presence of hSP-A1 allows surfactant to adopt a particularly favorable structure with optimal biophysical properties and helps to restore a proper behavior in the presence of an inhibitory agent as serum.