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

Abstract

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...

Aquaporin‐1 expression in the chick embryo chorioallantoic membrane

“…Our data concerning the immunoreactivity of the endothelium of CAM blood vessels to AQP1 suggest that also at this level AQP1 might be implicated in governing the water pathway through the endothelium, as has been established in the descending vasa recta (Pallone et al, 2000) and in microvessels of alveolar and distal airways (Bai et al, 1999). Moreover, in AQP1 knockout mice it has been shown that AQP1 provides a quantitatively important "exclusive water pathway" for osmotically induced water movement across the capillary endothelium (Yang et al, 1999), representing 10 -45% of the total transcellular hydraulic permeability of the microvascular wall (Renkin and Curry, 1982;Wolf and Watson, 1989).…”

Functions of aquaporins in the eye

“…In each of these systems the rate of transepithelial fluid secretion normalized to epithelial surface area is very high, such that the reduced but non-zero water permeability in AQP deficiency impairs transepithelial osmotic equilibration. In other epithelia, where areanormalized rates of fluid absorption/secretion are much lower, AQPs are not required for transepithelial fluid transport, as found for tear fluid secretion by lacrimal gland , sweat secretion (Song et al, 2002), alveolar fluid absorption (Bai et al, 1999;, and airway fluid absorption . Involvement of AQP-in the reduced tear fluid secretion in Sjogren's syndrome has been suggested (Tsubota et al, 2001), though subsequently refuted (Beroukas et al, 2001).…”

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

“…Water can travel through transcellular channels known as aquaporins. However, studies using specific aquaporin-null mice have demonstrated that these channels do not have significant roles in alveolar fluid absorption despite their importance in osmotically driven water movement across epithelial and endothelial cell barriers in the lung [10][11][12][13][14][15]. Cl − is secreted into the alveolar space via the cystic fibrosis transmembrane regulator (CFTR) [16]; this receptor also plays a role in cAMP-mediated fluid transport [17,18].…”