Perinatal changes in lung surfactant calcium measured in situ.

Abstract

Calcium ion is thought to play a role in the structure and function of pulmonary surfactant after secretion into the alveolar space. Since fetal lung liquid calcium concentration is inadequate for this hypothesized role, at a time when optimal surfactant function is necessary for survival, we speculated that the necessary calcium is secreted with the surfactant material, i.e., in the lamellar body. Lungs from rat fetuses at 20, 21, and 22 d gestation, and also from newborn rats at 3-5 h, 1 and 3 d, were rapidly frozen, sectioned, freeze-dried, and examined cold (-100°C) in a transmission electron microscope equipped with a fully quantitative energy-dispersive x-ray detector and analyzer. X-ray spectra were collected from the lamellar bodies and cytoplasm of type II cells at each time point. Lamellar body calcium concentration in the fetus was approximately twice that of the adult (70±4 vs. 37±2 mmol/kg dry wt±SEM, P < 0.01), and it decreased rapidly after birth to adult levels. Apically located lamellar bodies in the fetus have a significantly higher calcium concentration than those in a perinuclear position (76±4 vs. 52±3, P < 0.01). There is a significant correlation of calcium and chloride concentrations in lamellar bodies, suggesting that factors responsible for the distribution of chloride, i.e., pH, may also be responsible for the accumulation of calcium by these organelles. These results show that mature calcium transport in lamellar bodies is achieved prenatally in the rat, and suggest that the calcium required for normal surfactant function at birth is secreted with the lamellar body.

Effect of Acidic pH on the Structure and Lipid Binding Properties of Porcine Surfactant Protein A

“…Right, the internal pH of the subcellular compartments of the exocytic pathway (12,14) and pH of alveolar fluid. These subcellular compartments are exposed to high concentrations of calcium (13,14,16). The Ca 2ϩ concentration in the alveolar liquid is in the 1-2 mM range (25).…”

“…The regulated secretory pathway of the type II cell is atypical because the lamellar body not only functions as a classic secretory granule, but it also intersects with the endocytic pathway (10,11). Like the storage granules in other secretory cells, lamellar bodies have an acidic internal environment (pH 5.5) (12) and high calcium content, bringing their intravesicular free Ca 2ϩ concentration to a 2-10 mM range (13). It is well recognized that during the process of secretory granule formation, proteins of the granule content are segregated from proteins that are released from the cell by the constitutive secretory pathway.…”

Calcium Transport Across the Dental Enamel Epithelium

“…In the mammary gland, most calcium is thought to be extruded by co-secretion with milk proteins, and a substantial flux can be sustained (Neville and Watters, 1983), equivalent to about 50% of the intestinal calcium transport rate (Bronner et al, 1986). In the lung, calcium is co-secreted with lamellar bodies from alveolar cells (Eckenhoff, 1989). It is noteworthy that, in the mammary gland and lung, the major secreted proteins (caseins and surfactant protein-A, respectively) have calcium-binding properties (Haagsman et al, 1987) and so might enrich the secretory vesicles with calcium.…”

“…For example, fertilization is critically dependent on elevated calcium levels in the Fallopian tube (Leese, 1988;Mathieu et al, 1989b), and subsequent fetal development utilizes calcium transported across the placenta (Sibley, 1994). Breathing depends on calcium secreted into the lung fluid to maintain effective wetting properties of surfactant (Eckenhoff, 1989), calcium is secreted into milk by mammary epithelial cells (Neville and Watters, 1983), and calcium is required at high concentrations in thyroid follicles for thyroglobulin storage (Fonlupt et al, 1997). Much remains to be learned about the mechanisms used to transport calcium in these tissues, but some similarities with enamel epithelium are already evident.…”

Pulmonary surfactant and its apoproteins.

“…They also confirm the critical role of calcium in tubular myelin formation (45). Lamellar bodies may have a high total calcium content (46), suggesting that all the components required for tubular myelin may be assembled in the cell before secretion. The rapid hydration of lamellar body contents after secretion into fluid containing millimolar calcium ions may therefore be the essential step for their dramatic structural transformation.…”