JA Whitsett

Abstract

Mammalian pulmonary surfactants contain four distinct surfactant proteins, termed surfactant proteins A, B, C, and D (SP-A, SP-B, SP-C, and SP-D), that play unique roles in host defense, surfactant phospholipid homeostasis, and surfactant function. While in vitro studies supported overlapping roles for the surfactant proteins, unique functions for each surfactant protein were identified by studies in transgenic mice in which the surfactant proteins were deleted by gene targeting. Findings in transgenic mice lacking SP-A and SP-D demonstrated that each plays distinct roles in host defense, and in the regulation of surfactant structure and metabolism. Targeting of SP-B gene demonstrated its critical role in lung function after birth; mutations in the mouse or human SP-B gene caused respiratory failure in the immediate postnatal period. Likewise, mutations in the SP-C gene altered pulmonary function in mice. Thus, surfactant proteins play distinct and important roles in pulmonary function and host defense.