Conversion of lamellar body membranes into tubular myelin in alveoli of fetal rat lungs.

Abstract

Fluid-filled lumina of fetal rat lungs contain lamellar bodies (LBs) as well as tubular myelin (TM), both of which are thought to be stores of phospholipid-rich pulmonary surfactant. The alveolar epithelium is believed to secrete LBs, but neither the origin nor the mechanism of TM formation is entirely certain. The main objective of this study was to determine the relationship between secreted LBs and TM and to define membrane phenomena which occur during TM formation. I examined lung tissues of 20-21 day-old fetuses (day 22 = term) using transmission and high voltage transmission electron microscopy and cytochemistry. My findings indicate that secreted LBs, identified by the presence of an acid-phosphatase reactive core, are the precursor of TM. Secreted LBs are highly organized structures which contain structurally specialized areas, one of which is a "mini-lattice" structure similar to TM. During TM formation, fuzzes or 8.0-nm diameter particles appear on transition membranes, although LB membranes appear to lack both structures. Similar particles are present on TM membranes and are generally associated with membrane intersections. My results provide evidence that TM is formed from LBs within the alveolar lumen by mechanisms which may be complex.Abundant evidence suggests that pulmonary surfactant (surface-active material), a phospholipidrich material (5, 32, 33), forms an extracellular layer covering the alveolar epithelium. Numerous studies support the hypothesis that the surfactant prevents alveolar collapse at low lung volumes by decreasing alveolar surface tension; thus, the presence of surfactant is important in maintaining ~or-mal respiratory functions (10, 40). After their synthesis by type II epithelial cells (7,9,29,31), lamellar bodies, the intracellular form of surfactant (2, 6, 18), are secreted into the alveolar lumen as layers of membranes arranged in a spherical granule (43). To perform its proposed function, however, the lamellar body material must be arranged upon lung surfaces to form a phospholipid monolayer which is probably a continuous sheet-like film.Although the sequence of events which takes place in the rearrangement from lamellar form to monolayer has not been directly visualized, morphological, chemical, and physical observations (18,43,52,53) suggest that a second form of surfactant, tubular myelin, is generated within the alveolar lumen. Tubular myelin formation may therefore be an intermediate step in monolayer formation.As described by Weibel et al. (55), tubular myelin is composed of numerous tightly packed tubules whose walls have a trilaminate structure 260

Maintenance of surfactant protein A and D secretion by rat alveolar type II cells in vitro

“…Immunocytochemistry was performed as previously described (52,53), and electromicroscopy was done by standard techniques (51). Cells were immunostained for SP-D in acid alcohol-fixed cultures, embedded in paraffin, and localized with polyclonal rabbit anti-rat SP-D IgG and FITC-labeled donkey antirabbit IgG (Jackson ImmunoResearch Laboratories, West Grove, PA) (52).…”

Biogenesis of Multilamellar Bodies via Autophagy

“…MLBs are found in numerous cell types where they function in lipid storage and secretion (Schmitz and Mü ller, 1991). In lung type II alveolar cells, MLBs function as secretory granules whose exocytosis results in the deposition of the tubular myelin forms of surfactant on the surface of the alveolae (Hatasa and Nakamura, 1965;Ryan et al, 1975;Williams, 1977). The surfactant film over the alveolar epithelium regulates the surface tension at the air-cell interface and protects the alveola from collapse during respiration (Haagman and van Golde, 1991).…”

Human SP‐A and a pharmacy‐grade porcine lung surfactant extract can be reconstituted into tubular myelin – a comparative structural study of alveolar surfactants using cryo‐transmission electron microscopy

“…The spacing is somewhat irregular, probably due to high bilayer curvature, further discussed below. Williams (1977) in her pioneering study of TM formation observed periodicity along the ÔtransientÕ bilayers when LBs transform into TM. Particles were seen along one side of the bilayer with a diameter of about 8 nm, and a similar distance was reported to occur between particles.…”

“…at physiological conditions. In the previously mentioned studies (Nichols, 1976;Williams 1977;Young et al, 1992), chemical fixation was performed at room temperature, typically followed by post-fixation in osmium tetraoxide at 4°C and dehydration. At such fixation conditions, the hydrocarbon chain core of the lipid bilayer should crystallize (at least partly) according to a recent X-ray scattering/diffraction study .…”