The Clara cell of the mouse terminal bronchiole has been examined by high resolution phase contrast and electron microscopy, and the secretory route of surfactant in the mouse lung has been investigated using both light and electron microscopical autoradiography of a surf actant precursor (palmitic acid). Serial sections of terminal bronchioles examined by phase contrast microscopy demonstrated the appearances of apocrine secretion of amorphous droplets by Clara cells. Electron microscopy showed that the non-decapitating supranuclear region of Clara cells contained numerous rounded mitochondria with scanty achrestic cristae, whilst the apical portion was rich in smooth tubular membranes. Autoradiographical labeling of bronchiolar Clara cells exceeded that of all other cell types within three minutes of administration of the radioactive precursor, with location primarily over the endoplasmic reticulum. Subsequently there was heavy labeling of the bronchiolar lining layer. An hour later, silver grains were most numerous over the lamellated bodies of type I1 cells. It is suggested that palmitic acid is synthesized in the specialized mitochondria of the non-secretory region of the Clara cell and is incorporated into dipalmitoyl lecithin in the membranous apex. Subsequent secretion, possibly by the apocrine mechanism, provides a surface-active bronchiolar lining layer.The suggestion that surface tension is responsible for up to 75% of the elasticity of the mammalian lung was made by von Neergaard ('29) who compared the deflation pressurevolume curves of saline-filled lungs with air-filled lungs, and found marked hysteresis in the latter. Three decades elapsed before the presence of a highly surf ace-active extracellular alveolar lining layer became well documented. Therefore, there is much evidence that type 11 cells are responsible for surfactant secretion, but as Niden ('67) has indicated, the evidence is entirely circumstantial and could equally well support a phagocytic rather than secretory role for the type I1 cell. Finely divided thorium and carbon introduced via the trachea are incorporated into the lamellar bodies of type I1 cells in small amounts, implying either phagocytosis (Niden, '67), passive inflow of particles during the secretory process (Corrin, '69) or the possibility that type I1 cells represent a stage of lung macrophage development (Ladman and Finley, '66).Less attention has been given to Niden's suggested alternative site of surfactant production, namely the terminal bronchiole. The nonciliated epithelial cells were first described by Kolliker (1881) and later studied in detail by Clara ('37) after whom they are generally named. Clara concluded that these cells are specialized for the apocrine secretion of a non-mucoid substance, but further evidence to support an apocrine mode of secretion is sparse. and merocrine secretion to contain electron-dense secretory granules (von Spoendlin, '59; Wang et al., '71), abundant choline-based phospholipid, and many synthetic and energy-producing en...
