commentary review reports primary research AE2 = alveolar epithelial cell type II; BAL = bronchoalveolar lavage; GM-CSF = granulocyte-macrophage colony-stimulating factor; ICAM = intercellular cell-adhesion molecule; KGF = keratinocyte growth factor; MCP-1 = monocyte chemotactic polypeptide-1; RANTES = regulated on activation, normal T cell expressed and secreted; SP = surfactant protein; TGF = transforming growth factor; TNF = tumour necrosis factor; VCAM = vascular celladhesion molecule.Available online http://respiratory-research.com/content/2/1/033
IntroductionAs early as 1954, CC Macklin had postulated some of the most important functions of the great pneumocyte, ie the pneumocyte type II or alveolar epithelial type II (AE2) cell ( Fig. 1) [1]. Macklin presumed that these cells secrete material that provides low surface tension, enhances clearance of inhaled particles, is bacteriostatic, and helps prevent transudation of interstitial fluid into the alveolus. He further reported that these cells proliferate after lung injury by osmium tetroxide fumes [1]. By 1977, enough data had been collected to stimulate Mason and Williams [2] to formulate the concept of the AE2 cell as a "defender of the alveolus". It was established that the main functions were synthesis and secretion of surface-active material, hyperplasia in reaction to alveolar epithelial injury, and serving as the progenitor for AE1 cells, which form the epithelial component of the thin air-blood barrier. Nevertheless, several "postulated" functions were listed, for example, secretion of other substances, modulation of the alveolar hypophase, and adaptation in response to lung injury [2]. In the following 23 years, an increasing number of studies revealed many more details concerning the role of the AE2 cell in surfactant delivery and alveolar epithelial repair (see Supplementary Table 1) and a considerable number of supplementary functions have been established (see Supplementary Table 2). This review covers most aspects of current knowledge of AE2 cell functions.
The AE2 cell as the source of alveolar surfactant Composition of surfactantAlthough the presence of a surface-active agent in the mammalian lung was postulated by von Neergaard as early as 1929 [3], it was the work of Pattle Clements [5] that opened a new scientific field (for review of historical aspects, see [6]). This surface-active agent, termed surfactant, was characterised in numerous biochemical studies of bronchoalveolar lavage (BAL) material and is now known to be composed of ≈90% (mass) lipids (with ≈80-90% phospholipids) and of ≈10% proteins. Its composition may deviate greatly in pathologic states (for review, see eg [7]). Unlike most other lipid-rich components of cells and organs, the surfactant lipids are characterised by an unusually high level of saturated fatty acid chains, such as the predominant dipalmitoylphosphatidylcholines, which contribute substantially to the unique properties of pulmonary surfactant (for review, see eg [8]). The protein fraction comprises a hi...