Human Surfactant Proteins (SP-) A1 and SP-A2: to Include or Not in Surfactant Replacement Therapy, and If Yes, Both or Which One?

Abstract

Based on a large number of animal studies, surfactant protein A plays important roles in lung innate immunity under basal conditions and in response to various insults such as infection and oxidative stress. SP-A interacts with the Alveolar Macrophage (AM), the sentinel cell of innate immunity, and regulates many of its functions. These include the ability of the AM to produce cytokines and to carry out phagocytosis of various pathogens. Moreover, the AM proteomic expression profile has been shown to be significantly affected by SP-A. In a study where SP-A -/mice were treated (or rescued) in vivo with a single dose of human SP-A, the treatment nearly restored the AM proteomic expression to that of the wild type [1], supporting a role of SP-A on AM protein expression. Among the protein groups affected were actin-related/cytoskeletal proteins, which was the major group, proteins regulating inflammatory processes, and proteins related to Nrf2-mediated oxidative stress. Of interest, earlier studies have also indicated a role for SP-A in actin filament dynamics via its ability to enhance cell migration and AM chemotaxis [2], phagocytosis [3], other actin-dependent processes [4-6] and F-actin assembly [7]. The actin cytoskeleton is highly regulated and dynamic, with globular (G) and filamentous (F) actin, under the influence of many actin binding proteins, constantly changing by polymerization, depolymerization, branching, and remodeling, modulating inflammatory response and oxidative stress (Figure 1).