Genetic Diversity of Human SP-A, a Molecule with Innate host Defense and Surfactant-Related Functions; Characteristics, Primary Function, and Significance

Abstract

Pulmonary surfactant, a lipoprotein complex, is essential for life. It lowers the surface tension at the air-liquid interphase of the distal lung airspaces (alveoli) to prevent alveolar collapse at low lung volumes. Alveolar stability is critical in maintaining a normal O2/CO2 exchange. Surfactant deficiency in the prematurely born infant can lead to respiratory problems or respiratory distress syndrome (RDS); a major complication of infants with RDS is infection. Surfactant dysfunction has been associated with several pulmonary diseases characterized with impaired O2/CO2 exchange, deranged inflammatory processes and host defense. Pulmonary surfactant consists of approximately 90% lipids, with phospholipids constituting the major lipid component, and about 10% of proteins with surfactant protein A (SP-A) found in great abundance. SP-A has been identified with several diverse functions. Broadly, these include surfactantrelated and host defense-related functions. Human SP-A is encoded by two genes, SP-A1 and SP-A2, and exhibits extensive complexity at the DNA, RNA, and protein level, compared to rodent SP-A and even to that of the primates. Although, the significance of such complexity is not currently understood, a number of studies have revealed associations between certain SP-A variants or levels of SP-A and pulmonary disease. Moreover, functional, structural, and biochemical differences have been observed between in vitro expressed SP-A1 and SP-A2 variants. We speculate that the human SP-A complexity provides diversity in the overall SP-A functional activities. We suggest that because of its complexity, which appears to translate in quantitative and qualitative differences among individuals, SP-A can provide a good model for study of the basis of individual variability to disease susceptibility and/or to drug response. In this paper, we review types of SP-A complexity and comment on the significance of such variability, summarize associations between SP-A genetic variants and pulmonary diseases, and speculate on the SP-A primary function (surfactant or the host defense) by discussing a number of attributes. The focus of this mini review is on the human SP-A genes and alleles.