Regulation of lung surfactant secretion

Chander, Avinash; Fisher, Aron B.

doi:10.1152/ajplung.1990.258.6.l241

Cited by 121 publications

(98 citation statements)

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“…Though the morphometric studies about the number of LB in type II alveolar cells are very scant (Kliewer et al, 1985), the decreasing of LB per type II pneumocyte has been considered a direct expression of increased surfactant secretion in mammals (Chander and Fisher, 1990). Taking into account that, in the present study, the main difference between the two pigeon groups has been living in a polluted or nonpolluted habitat, air pollutants must be the cause of the pulmonary disturbance revealed in our results (i.e., the decrease of LB in the city animals).…”

Section: Discussionmentioning

confidence: 99%

Incidence of air pollution in the pulmonary surfactant system of the pigeon (Columba livia)

Lorz

López

1997

Anat. Rec.

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Background: The integrity of both pulmonary surfactant and surfactant producing cells, type II pneumocytes, is essential for normal pulmonary function. Almost all studies about air pollution effects on the pulmonary surfactant system have been performed by biochemical techniques, using atmospheric pollutants in a much higher concentration than that found in polluted city air. A comparative study of the number of lamellar bodies (LB) (pulmonary surfactant precursors) from type II pneumocytes of pigeon lungs belonging to a contaminated city habitat and a noncontaminated countryside one has been carried out.Methods: Lungs of both pigeon groups were subjected to standard processing for light microscopy. A representative number of histological sections from each lung were stained by Gomori's methenamine-silver nitrate technique, which appears to be a good marker for pulmonary LB. Diverse areas of atrial and parabronchial epithelia from each section were photographed, and then quantification of the number of LB per type II pneumocyte section was performed. The data were statistically analyzed and compared on the basis of the levels of atmospheric pollutants.Results: Gomori's methenamine-silver nitrate technique is a useful staining method to study pneumocyte LB. The average of LB per cell section in city birds was about 33% less than in countryside specimens. Moreover, a great amount of macrophages in the lungs from city pigeons has been shown to be present, whereas this cell type is absent or very scarce in the lungs from country birds.Conclusions: Solid particles and high rates of nitrogen oxides in the polluted air, as well as the oxygen metabolites produced by the macrophages, would represent the main factors for the marked decrease in the amount of LB from type II pneumocytes. Anat.

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Section: Discussionmentioning

confidence: 99%

Incidence of air pollution in the pulmonary surfactant system of the pigeon (Columba livia)

Lorz

López

1997

Anat. Rec.

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“…The net effect of the hSP-B ⌬c transgene correction in SP-B(Ϫ/Ϫ) mice likely reflects regulation of the alveolar pool to maintain normal surfactant homeostasis. Many mechanisms that promote surfactant secretion have been described (35); however, very little is known about pool size regulation. Other transgenic models indicate that cytokines such as granulocytemacrophage colony-stimulating factor are produced by type II cells and can modulate surfactant component clearance kinetics (17,36).…”

Section: Function Of Sp-b Propeptidementioning

confidence: 99%

Rescue of SP-B Knockout Mice with a Truncated SP-B Proprotein

Akinbi

Breslin

Ikegami

et al. 1997

Journal of Biological Chemistry

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Pulmonary surfactant is a complex mixture of lipids and proteins that is synthesized exclusively by the alveolar type II epithelial cell. Surfactant is stored in large inclusions (lamellar bodies) that are secreted into the alveolar airspace by exocytosis. Newly secreted lamellar bodies unravel into a tubular network (tubular myelin) that subsequently adsorbs and spreads as a phospholipid-rich film that reduces surface tension at the air-liquid interface. Rapid adsorption and spreading of the phospholipid film are critical and require the presence of specific proteins, in particular surfactant proteins B and C (1-3).Surfactant protein B (SP-B) 1 is a hydrophobic peptide of 79 amino acids that avidly associates with surfactant phospholipids in the alveolar airspace (reviewed in Ref. 4). Homozygous mutations leading to the complete absence of SP-B in newborn human infants result in the rapid onset of respiratory distress syndrome which is refractory to mechanical ventilation and surfactant replacement (5, 6). The latter observation suggests that simple addition of mature peptide to the SP-B-deficient airway is not sufficient to restore lung function. Therefore, despite an obvious requirement for SP-B in normal lung function, the precise role(s) of SP-B in the structure, function, and metabolism of surfactant remains unclear.Human SP-B is synthesized by the type II epithelial cell as a preproprotein of 381 amino acids. The mature peptide is generated by sequential cleavage of the signal peptide (23 amino acids), the N-terminal propeptide (177 residues), and the Cterminal propeptide (102 residues) (7, 8). Propeptide cleavage occurs within the late endosome/multivesicular body which subsequently directs newly synthesized SP-B to the lamellar body (9); mature SP-B is also recycled from the alveolar airspace, via the endocytic pathway to the multivesicular body (10). Previous in vitro evidence supports the concept that trafficking of the mature peptide through the biosynthetic pathway requires the N-terminal but not the C-terminal domain of the propeptide (11,12). In the absence of both propeptide domains the mature peptide is degraded within the endoplasmic reticulum (11); however, an SP-B construct encoding both the Nterminal propeptide and the mature peptide (hSP-B ⌬c ) produces a truncated proprotein that is sorted to the multivesicular body where the propeptide is appropriately cleaved to liberate mature SP-B (12). These results clearly demonstrate that the N-terminal propeptide is required for the intracellular trafficking of SP-B; the function of the C-terminal propeptide, however, remains unknown.Lung morphogenesis and surfactant phospholipid synthesis in SP-B(Ϫ/Ϫ) mice proceed normally prior to birth (13). However, lamellar body formation is disrupted, resulting in abnormal inclusions consisting of multivesicular bodies and disorganized lamellae. Neither mature lamellar bodies nor tubular myelin were detected in the SP-B(Ϫ/Ϫ) mice. In addition to effects on lamellar body biogenesis, SP-B deficiency resulted in

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“…It is well known that surfactant deficiency causes respiratory distress syndrome (RDS) 2 in preterm infants (1)(2)(3)(4)(5). Glucocorticoid is administered prenatally to prevent RDS by promoting maturation of the surfactant system, and surfactant replacement is widely used to treat RDS (6,7).…”

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confidence: 99%

ABCA3 as a Lipid Transporter in Pulmonary Surfactant Biogenesis

Ban

Matsumura

Sakai

et al. 2007

Journal of Biological Chemistry

203

130

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ABCA3 protein is expressed predominantly at the limiting membrane of the lamellar bodies in alveolar type II cells, and mutations in the ABCA3 gene cause lethal respiratory distress in newborn infants. To investigate the function of ABCA3 protein, we generated Abca3-deficient mice by targeting Abca3. Fullterm Abca3؊/؊ newborn pups died within an hour after birth because of acute respiratory failure. Ultrastructural analysis revealed abnormally dense lamellar body-like organelles and no normal lamellar bodies in Abca3 ؊/؊ alveolar type II cells. TLC and electrospray ionization mass spectrometry analyses of lipids in the pulmonary interstitium showed that phosphatidylcholine and phosphatidylglycerol, which contain palmitic acid and are abundant in normal surfactant lipids, were dramatically decreased in Abca3 ؊/؊ lung. These findings indicate that ABCA3 plays an essential role in pulmonary surfactant lipid metabolism and lamellar body biogenesis, probably by transporting these lipids as substrates.

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Regulation of lung surfactant secretion

Cited by 121 publications

References 0 publications

Incidence of air pollution in the pulmonary surfactant system of the pigeon (Columba livia)

Incidence of air pollution in the pulmonary surfactant system of the pigeon (Columba livia)

Rescue of SP-B Knockout Mice with a Truncated SP-B Proprotein

ABCA3 as a Lipid Transporter in Pulmonary Surfactant Biogenesis

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