Developmental changes in water permeability across the alveolar barrier in perinatal rabbit lung.

Carter, E P; Umenishi, Fuminori; Matthay, Michael A.; Verkman, A. S.

doi:10.1172/jci119617

Cited by 51 publications

(34 citation statements)

References 57 publications

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“…As explained in the Introduction, several lines of indirect evidence suggest, but do not prove, that aquaporins play a role in lung physiology: aquaporins are expressed in lung epithelia and endothelia (13)(14)(15)(16)(17); water permeability is high in epithelia and endothelia where aquaporins are expressed (13,(22)(23)(24); and aquaporin expression (18)(19)(20) and function (21) increase near the time of birth. Analysis of the phenotype of aquaporin knockout mice enables direct examination of the functional role of aquaporins in lung.…”

Section: Discussionmentioning

confidence: 99%

“…The specific localization of aquaporins to endothelial and epithelial cells suggests a role in water movement between airspace, interstitial, and capillary compartments. Other indirect evidence supporting a physiological role for aquaporins in lung includes the increase in aquaporin expression (18)(19)(20) and lung water permeability (21) around the time of birth, and the high water permeability of alveolar (13,22), microvascular (23), and airway (24) barriers. Recently, immunopurified type I alveolar epithelial cells were found to have an exceptionally high water permeability, with biophysical properties indicative of molecular water channels (25).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice

Bai¹,

Fukuda²,

Song³

et al. 1999

J. Clin. Invest.

222

163

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Substantial quantities of fluid move across epithelial and endothelial barriers in lung. In the perinatal lung, fluid absorption from the airspaces occurs in preparation for alveolar respiration (1). In the adult lung, movement of salt and water between the airspace and capillary compartments is required for control of airspace hydration. The formation and resolution of clinical pulmonary edema involve fluid movements among the airspace, interstitial, and capillary compartments (2-4). Considerable progress has been made in understanding the molecular mechanisms of salt movement between the airspace and capillaries. Recent work has begun to define the role of the ENaC sodium channel (5), the ClC-2 and CFTR Cl -channels (6, 7), and the Na + /K + pump (8, 9).There have been recent advances in understanding the molecular mechanisms of water movement in lung. A family of (currently) 10 related molecular water channels called aquaporins has been identified in mammals (reviewed in refs. 10-12). The aquaporins are small hydrophobic membrane proteins (M r ∼30,000) with homology to the major intrinsic protein of lens fiber. Three aquaporins have been localized in lung: AQP1 in microvascular endothelia and some pneumocytes (13-15), AQP4 in the basolateral membrane of airway epithelium (16), and AQP5 in the apical membrane of type I alveolar epithelial cells (17). Aquaporin-type water channels have not yet been identified at the basolateral surface of alveolar epithelium or at the apical membrane of airway epithelia. The specific localization of aquaporins to endothelial and epithelial cells suggests a role in water movement between airspace, interstitial, and capillary compartments. Other indirect evidence supporting a physiological role for aquaporins in lung includes the increase in aquaporin expression (18)(19)(20) and lung water permeability (21) around the time of birth, and the high water permeability of alveolar (13,22), microvascular (23), and airway (24) barriers. Recently, immunopurified type I alveolar epithelial cells were found to have an exceptionally high water permeability, with biophysical properties indicative of molecular water channels (25).We have developed quantitative pleural surface fluorescence methods to measure osmotic water permeability of the airspace-capillary barrier (22) The mammalian lung expresses water channel aquaporin-1 (AQP1) in microvascular endothelia and aquaporin-4 (AQP4) in airway epithelia. To test whether these water channels facilitate fluid movement between airspace, interstitial, and capillary compartments, we measured passive and active fluid transport in AQP1 and AQP4 knockout mice. Airspace-capillary osmotic water permeability (P f ) was measured in isolated perfused lungs by a pleural surface fluorescence method. P f was remarkably reduced in AQP1 (-/-) mice These results indicate that osmotically driven water transport across microvessels in adult lung occurs by a transcellular route through AQP1 water channels and that the microvascular endothelium is a significant ba...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice

Bai¹,

Fukuda²,

Song³

et al. 1999

J. Clin. Invest.

222

163

View full text Add to dashboard Cite

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“…The mRNA and protein expression of AQPs appears late in gestation, increases markedly at birth, and remains elevated during early postnatal life (9,10). This developmental pattern of AQP expression parallels perinatal changes in the osmotic water permeability of the lung and the rate of lung water removal that occurs around birth (11).…”

mentioning

confidence: 81%

Lung Water and Proton Magnetic Resonance Relaxation in Preterm and Term Rabbit Pups: Their Relation to Tissue Hyaluronan

et al. 2000

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The present study was performed to investigate simultaneously total lung water, T 1 and T 2 relaxation times, and hyaluronan (HA) in preterm and term rabbits. Attempts were also made to establish the relationship of HA to total lung water and to T 2 -derived motionally distinct water fractions. Experiments were performed in fetal Pannon white rabbit pups at gestational ages of 25, 27, 29, and 31 d and at a postnatal age of 4 d. Lung tissue water content (desiccation method), T 1 and T 2 relaxation times (H 1 -NMR method), and HA concentration (radioassay) were measured, and free and bound water fractions were calculated by using multicomponent fits of the T 2 relaxation curves. Lung water content and T 1 and T 2 relaxation times were highest at a gestational age of 27 d and then declined steadily during the whole study period. Similar trends and time courses were seen for the fast and slow components of the T 2 relaxation curve. The T 2 -derived free water fraction remained unchanged at a gestational age of 25-29 d (ϳ67%), but increased progressively to a value of 78.5 Ϯ 7. During fetal life the potential air space of the lung is filled with fluid, which is generated by continuous epithelial secretion driven by active chloride transport. As parturition approaches, the lung fluid secretion decreases, and sodium transport-dependent reabsorption begins. This switch in transepithelial water movement culminates at birth and results in rapid clearance of lung fluid, which is critical for successful transition to air breathing (1-4).The osmotic water permeability of the alveolar epithelium is developmentally regulated by and related to the expression of water-transporting proteins, called AQPs. Three AQPs have been identified in the lung: AQP1 in the capillary endothelium, AQP4 in the basolateral membrane of the airway epithelium, and AQP5 in the apical membrane of alveolar epithelial type I cells (5-8).The specific localization of AQPs to endothelial and epithelial cells suggests water movement between the air space and the interstitial and capillary compartments. It takes place through individual water channels. The mRNA and protein expression of AQPs appears late in gestation, increases markedly at birth, and remains elevated during early postnatal life (9, 10). This developmental pattern of AQP expression parallels perinatal changes in the osmotic water permeability of the lung and the rate of lung water removal that occurs around birth (11).In addition to active ion transport-driven AQP-mediated water transport, the physical state of tissue water is also an important determinant of perinatal lung water clearance. Namely, a fraction of tissue water is motionally constrained, i.e. bound to macromolecules and thus made unavailable for immediate transport across alveolar, microvascular, and airway barriers (12).

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“…The high water permeability of type I cells, together with previous studies of water channel expression and function in the lung, suggest an important role for aquaporin-type water channels in lung physiology. Water channels are expressed strongly in airway and alveolar epithelial and endothelial plasma membranes (5-9), water permeability is high across alveolar (5,6) and airway (35) epithelia, and lung water channel expression (36,37) and function (38) are developmentally regulated. Studies of lung functions in transgenic mice lacking specific water channels may help to define the precise roles of aquaporins in pulmonary physiology in normal and diseased states.…”

Section: ϫ2mentioning

confidence: 99%

Highly water-permeable type I alveolar epithelial cells confer high water permeability between the airspace and vasculature in rat lung

Dobbs

Gonzalez

Matthay

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

205

138

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Water permeability measured between the airspace and vasculature in intact sheep and mouse lungs is high. More than 95% of the internal surface area of the lung is lined by alveolar epithelial type I cells. The purpose of this study was to test whether osmotic water permeability (P f ) in type I alveolar epithelial cells is high enough to account for the high P f of the intact lung. P f measured between the airspace and vasculature in the perfused f luid-filled rat lung by the pleural surface f luorescence method was high (0.019 ؎ 0.004 cm͞s at 12°C) and weakly temperature-dependent (activation energy 3.7 kcal͞mol). To resolve the contributions of type I and type II alveolar epithelial cells to lung water permeability, P f was measured by stopped-f low light scattering in suspensions of purified type I or type II cells obtained by immunoaffinity procedures. In response to a sudden change in external solution osmolality from 300 to 600 mOsm, the volume of type I cells decreased rapidly with a half-time (t 1/2 ) of 60-80 ms at 10°C, giving a plasma membrane P f of 0.06-0.08 cm͞s. P f in type I cells was independent of osmotic gradient size and was weakly temperature-dependent (activation energy 3.4 kcal͞mol). In contrast, t 1/2 for type II cells in suspension was much slower, Ϸ1 s; P f for type II cells was 0.013 cm͞s. Vesicles derived from type I cells also had a very high P f of 0.06-0.08 cm͞s at 10°C that was inhibited 95% by HgCl 2 . The P f in type I cells is the highest measured for any mammalian cell membrane and would account for the high water permeability of the lung.Rapid water movement between the airspace and blood compartments of the lung is important in normal physiological processes such as the transition from an intrauterine to air environment and in pathological processes such as the formation and resolution of pulmonary edema. Water movement also may be important in maintaining lung water homeostasis. Between the air and the vasculature there are epithelial, interstitial, and endothelial compartments. The alveolar epithelium, which covers more than 99% of the internal surface area of the lungs (1), is comprised of a monolayer of two morphologically distinct types of cells, type I cells and type II cells. The very thin cytoplasmic extensions of type I cells cover 95-98% of the surface area of the lung (2). Type II cells, which cover the remaining 2-5% of the alveolar surface, are cuboidal cells best known for their ability to synthesize, secrete, and recycle components of pulmonary surfactant. The interstitial compartment varies considerably in thickness; at its thinnest, the alveolar epithelium is separated from capillary endothelium only by a fused basement membrane (3). Intercellular tight junctions between alveolar epithelial cells are thought to provide a tight barrier between the air and blood compartments of the lung (4). Based on these anatomic considerations, we postulated that alveolar epithelial type I cells might play an important role in water transport.Recent data indicate t...

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Developmental changes in water permeability across the alveolar barrier in perinatal rabbit lung.

Cited by 51 publications

References 57 publications

Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice

Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice

Lung Water and Proton Magnetic Resonance Relaxation in Preterm and Term Rabbit Pups: Their Relation to Tissue Hyaluronan

Highly water-permeable type I alveolar epithelial cells confer high water permeability between the airspace and vasculature in rat lung

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