Surfactant and lung inflammation

The thin alveolar lining consists of a single layer of epithelial cells and an overlay of an oily substance, the pulmonary surfactant, which contains surfactant proteins (SPs) (10% w/w) and lipids (90% w/w). In addition to the well established ability of the surfactant system to reduce alveolar surface tension and thereby prevent collapse of the alveoli on expiration, it is also involved in the very efficient removal of microbes and their debris,^1–3 dying epithelial cells, and phagocytes.⁴ The therapeutic use of exogenous surfactant is well established and has been shown to be effective in the treatment of premature infants with respiratory distress syndrome. The surfactant preparations normally used are natural surfactants of porcine (Curosurf) or bovine (Alveolfact, Survanta) origin, or synthetic protein free preparations. Surfactant preparations derived from natural sources contain the hydrophobic peptides SP-B and SP-C but none—or very low levels—of the much larger hydrophilic surfactant proteins SP-A and SP-D which are lost during the extraction procedure. Although surfactant lipids may reduce lung inflammation, recent studies suggest that these hydrophilic proteins are the major anti-inflammatory components of pulmonary surfactant.

EXISTING SURFACTANT THERAPY

Over the past 10 years it has become recognised that SP-A and SP-D—members of the innate immune collectin family of proteins which are secreted by type II alveolar epithelial cells—play important host defence and immunomodulatory functions in the surfactant system.^5,6 SP-A (~90% w/w of SPs) and SP-D (~3% w/w of SPs) are the major surfactant proteins and are involved in maintaining an infection-free and inflammation-free lung.^7,8 During acute lung infections these innate immune molecules can kill⁹ and/or opsonise and enhance the phagocytosis of microbes by freshly recruited phagocytes. …