The pulmonary extracellular lining.

George, Gerwyn; Hook, Gary E. R.

doi:10.1289/ehp.8455227

Cited by 18 publications

(5 citation statements)

References 150 publications

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“…Despite the sustained [Ca 2ϩ ] c , which did not fully revert to precontact levels, there were no signs of cell damage. We assume that evaporative water loss forces cell structures, such as the glycocalyx and other macromolecules that extend into the extracellular space, into ultimate close distances to the interface, probably beyond a remaining hydration shell (20). This configuration is highlighted by the distortion of interference fringes at the site of a cell.…”

Section: Resultsmentioning

confidence: 99%

“…Numerous ultrastructural and microscopic analyses also tell that AT II cells are cuboideal and preferably located near the septal corners with their apical side extending lumenal (41,52). A few investigations exist suggesting that AT II cells, including their microvilli, are entirely submerged by the ALF, which is even bulged into the alveolar lumen at the cell apex (5,20). Taking these facts and evidence together, a picture of an interfacial environment, sketched in Fig.…”

Section: Discussionmentioning

confidence: 99%

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Interfacial sensing by alveolar type II cells: a new concept in lung physiology?

Ravasio

Hobi²,

Bertocchi³

et al. 2011

American Journal of Physiology-Cell Physiology

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Alveolar type II (AT II) cells are in close contact with an air-liquid interface (IAL). This contact may be of considerable physiological relevance; however, no data exist to provide a satisfying description of this specific microenvironment. This is mainly due to the experimental difficulty to manipulate and analyze cell-air contacts in a specific way. Therefore, we designed assays to quantify cell viability, Ca 2ϩ changes, and exocytosis in the course of interface contact and miniaturized IAL devices for direct, subcellular, and real-time analyses of cell-interface interactions by fluorescence microscopy or interferometry. The studies demonstrated that the sole presence of an IAL is not sensed by the cells. However, when AT II cells are forced into closer contact with it, they respond promptly with sustained Ca 2ϩ signals and surfactant exocytosis before the occurrence of irreversible cell damage. This points to a paradoxical situation: a potential threat and potent stimulus for the cells. Furthermore, we found that the signalling mechanism underlying sensation of an I AL can be sufficiently explained by mechanical forces. These results demonstrate that the IAL itself can play a major, although so-far neglected, role in lung physiology, particularly in the regulatory mechanisms related with surfactant homeostasis. Moreover, they also support a general new concept of mechanosensation in the lung. mechanical stress; pneumocytes; strain; stretch; surfactant THE ALVEOLAR EPITHELIUM is covered by a thin and continuous layer of water (5). This aqueous layer, referred to as hypophase or alveolar lining fluid (ALF), introduces a considerable physical instability to the millions of alveolar invaginations, tending on overall to force the air out of the lungs. As a consequence, the great alveolar corner cells (or alveolar type II cells; AT II) synthesize and release surfactant into the ALF, from where it transits to the air-liquid interface (I AL ) and creates a highly surface-active coat (40). The importance of this protective coat is best demonstrated in the premature infant lung, where deficiency causes alveolar collapse with life-threatening consequences unless medicated by surfactant administration strategies (17).An important and almost unique aspect of the AT II cellspecific microenvironment is the presence of air. Not astonishingly, therefore, studies introducing such an I AL in AT II cell culture systems reported dramatic effects on cell function, morphology, protein expression, and ion channel activities (13,29). In general, the AT II cells have a higher phenotypic stability and seem to preserve characteristic cell functions for longer periods than compared with standard culture conditions. In particular, biosynthesis and secretion of surfactant is stable over several weeks. Furthermore, reculturing with exposure to air reverses the loss of differentiated AT II cell phenotype observed in submerged cultures (13). This effect of an I AL is indeed remarkable, though not readily intelligible. In particular, the phy...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interfacial sensing by alveolar type II cells: a new concept in lung physiology?

Ravasio

Hobi²,

Bertocchi³

et al. 2011

American Journal of Physiology-Cell Physiology

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“…and increased transaminase activity in the lungs of furfural-exposed rats are in agreement with earlier report^.^,^' In addition, enhanced activity of acid phosphatase confirms parenchymal injury/lysosomal damage22 and the elevated activity of alkaline phosphatase is indicative of regenerative proliferation of type I1 pneumocytes for which alkaline phosphatase is a marker enzyme. 23 The observed inhibition of arginase after exposure to furfural vapours reflects hampered mitochondria1 oxidative metabolism in rat lungs. This is corroborated by increased pulmonary lactate content and together these observations suggest a shift towards anaerobic metabolic pathways.…”

Section: Discussionmentioning

confidence: 98%

Inhalation toxicity of furfural vapours: An assessment of biochemical response in rat lungs

Gupta

Misra

Agarwal

1991

J of Applied Toxicology

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The pulmonary biochemical response, particularly the effects on mixed-function oxidases, was investigated in rats exposed to 40 ppm furfural for 1 h daily, 5 days per week, for periods of 7, 15 and 30 days. This concentration is ca. 22% of the acute LC50 dose. Exposure to furfural increased the activities of acid and alkaline phosphatases and glutamic-pyruvic transaminase, inhibited the activities of arginase and succinic dehydrogenases and elevated the concentration of lactic acid in the lungs. In the group of mixed-function oxidases, the activities of aminopyrene-N-demethylase and aniline hydroxylase (phase I, cytochrome P-450b specific) significantly increased and the activity of Benzo[a]pyrene hydroxylase (phase I, cytochrome P-450c specific) decreased. The activity of glutathione-S-transferase (phase II component) also was increased concurrently with a decrease in the concentration of glutathione. The magnitude of biochemical alterations in most cases was related directly to the duration of exposure. Our observations indicate that furfural caused pulmonary irritation, parenchymal injury and the regenerative proliferation of type II pneumocytes. Selective (cellular and/or cytochrome P-450 isozyme specific) enhancement of pulmonary mixed-function oxidases by furfural appears to stimulate its own pulmonary biotransformation, and the excretion of oxidative metabolites was facilitated by their enzymatic conjugation with glutathione.

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“…As for SP-B, it is presumed that the 23-residue N-terminal and [65]. It is generally accepted that the Type II cell is the site of surfactant synthesis [66].…”

Section: Sp-cmentioning

confidence: 99%

“…It is generally accepted that the Type II cell is the site of surfactant synthesis [66]. Within the Type II cell, surfactant is stored in secretory granules (lamellar bodies) whose lipid composition is similar to that of extracellular surfactant [65]. At least two surfactant proteins, SP-A and SP-B, have been localized to the lamellar body with monospecific antisera [67][68][69][70]; SP-C was also detected in a lamellar body enriched fraction of lung tissue by Western blotting [71].…”

Section: Sp-cmentioning

confidence: 99%

Function and regulation of expression of pulmonary surfactant-associated proteins

Weaver

Whitsett

1991

Biochemical Journal

388

264

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INTRODUCTIONThe respiratory tree of the lung consists of a graduated series of conducting airways that terminate distally in the alveoli. Gas exchange occurs across the alveolar epithelium during alternate expansion (inspiration) and contraction (expiration) of the alveoli. The collapsing forces that narrow the alveolar diameter during expiration are the product of elastic tissues within the alveolar interstitial wall, and surface tension generated by a thin aqueous film on the surface of the alveolar epithelium. The dramatic increase in surface tension at end expiration poses a major obstacle to alveolar stability at low lung volumes and makes inflation of the lung much more difficult. This potential problem is overcome by the juxtaposition of a complex mixture of lipids and proteins, pulmonary surfactant, at the interface of the aqueous film and air within the alveolar lumen. The specialized structure of the surfactant allows dense packing of the lipid film during expiration, thereby opposing the surface tension generated by the aqueous subphase. In the absence of pulmonary surfactant, increased surface tension along the alveolar epithelium results in alveolar collapse and epithelial cell lysis culminating in respiratory distress syndrome (RDS), a major cause of morbidity and mortality in preterm infants. Treatment of RDS frequently requires respiratory support in order to achieve effective gas exchange. In recent years, the advent of replacement surfactant mixtures as a therapy for RDS has reduced the requirement for respiratory support and significantly improved the short-term outcome of infants suffering from RDS.Pulmonary surfactant is composed of approximately 90 % lipid, 10 % protein and small amounts of carbohydrate. Dipalmitoylphosphatidylcholine (DPPC), which accounts for approximately half the lipid in surfactant, is primarily respoinsible for the surface tension reducing property of the surfactant complex. The synthesis, secretion and metabolism of DPPC and other surfactant lipids has been the subject of several recent reviews [1][2][3][4][5]. Specific surfactant proteins, SP-A, SP-B and SP-C, closely associated with surfactant lipids, contribute to the surfactant properties of the phospholipids. Recent studies suggest that surfactant-associated proteins may play other important roles in surfactant biology. The surfactant proteins have been the subject of several recent reviews [6][7][8] and the reader is directed to a review by Possmayer [8] for an historical perspective of the subject. The present review will focus on recent studies that provide insight into the regulation of expression and function of surfactant-associated proteins.

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The pulmonary extracellular lining.

Cited by 18 publications

References 150 publications

Interfacial sensing by alveolar type II cells: a new concept in lung physiology?

Interfacial sensing by alveolar type II cells: a new concept in lung physiology?

Inhalation toxicity of furfural vapours: An assessment of biochemical response in rat lungs

Function and regulation of expression of pulmonary surfactant-associated proteins

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