Decreased pulmonary vascular permeability in aquaporin-1-null humans

Abstract

The molecular determinants of water permeability in the human lung are incompletely defined. Aquaporins (AQP) are water-specific membrane channel proteins. AQP1 is present in endothelial cells in the lung, including those in the vascular plexus around the airways. Rare individuals have been identified who are deficient in AQP1. High-resolution computed tomography scans of the lung were used to evaluate the response to i.v. fluid challenge in two unrelated AQP1-null individuals and five normal controls. The airways and pulmonary vessels were measured at baseline and after i.v. administration of 3 liters of saline. Increases in airway wall thickness after fluid administration reflect peribronchiolar edema formation. Both control and AQP1 null subjects had approximately a 20% increase in pulmonary vessel area in response to saline infusion, suggesting similar degrees of volume loading. Control subjects had a 44% increase in the thickness of the airway wall, consistent with peribronchiolar edema formation. In marked contrast, airway wall thickness did not change in AQP1-null subjects in response to saline infusion. These studies indicate that AQP1 is a determinant of vascular permeability in the lung, and demonstrate a role for aquaporins in human pulmonary physiology. R egulation of water movement between the vascular, interstitial, and airway compartments is critical for normal lung function. Disruption of this process contributes to alterations in gas exchange, lung mechanics, and local lung defense mechanisms. However, the molecular determinants of water transport in the respiratory tract remain incompletely defined, particularly for human pathophysiology.Aquaporin-1 (AQP1), the archetypal membrane water channel protein, was initially described in red blood cells and renal proximal tubule epithelium (1). An extracellular epitope of AQP1 defines the Colton blood group antigen on red blood cells (2). Screening for anti-Colton antibodies by the International Blood Group Reference Laboratory identified only six Coltonnull kindreds worldwide; a seventh individual has recently been described (3). Individuals in three of these kindreds were evaluated, and each was found to be homozygous for a different mutation in the AQP1 gene with complete absence or marked reduction of AQP1 in red blood cell membranes (4). These individuals are unable to receive blood transfusions from normal donors, but otherwise reported no clinical symptoms as a consequence of AQP1 deficiency. Recent investigation of two AQP1-null individuals, however, revealed a decreased ability to concentrate urine maximally (5).AQP1 is abundantly expressed in pulmonary vascular endothelium, particularly in endothelial cells of the vascular plexus around the airways (6). This distribution suggests a role for AQP1 in regulation of vascular water permeability in the lung. In the present study, we provide the first functional assessment of any aquaporin in human lung. By using high-resolution computed tomography (HRCT) to examine the response to fluid challenge, ...

Water Channels (Aquaporins) and Their Role for Postnatal Adaptation

“…Because rodent lung epithelium appears to be more leaky than the human, the requirements for a regulated water transport should be more stringent in humans (59). Studies in human AQP1-null individuals have established that AQP1 is a determinant of vascular permeability in the lung (60). Furthermore, the distribution of AQPs in human lung has been reported to be different from that in rodents (61).…”

Downregulation of aquaporins 1 and 5 in nasal gland by osmotic stress in ducklings,Anas platyrhynchos: implications for the production of hypertonic fluid

“…Both bands were also detected in membrane preparations of mouse lung used as a reference, since mammalian lung cells express AQP1 at high levels King et al, 2002). Deglycosylation of solubilized membrane proteins from untreated nasal gland and from mouse lung using Nglycosidase F resulted in loss of signal intensity in the 35·kDa band and in a concomitant increase in signal intensity in the 28·kDa band, indicating that the higher molecular mass bands represent glycosylated forms of AQP1 (Fig.·3A).…”

Protective effect and mechanism of hydrogen treatment on lung epithelial barrier dysfunction in rats with sepsis

“…Recent discoveries have shown that the water permeability of the alveolar air space and capillary spaces in AQP-1-knockout mice decreases ten-fold compared with that of the wild-type mice (Bai et al, 1999;Song et al, 2000), while a 14-to 16-fold decrease is observed in AQP-1/ AQP-4-knockout mice (Song et al, 2000). King et al (2002) discovered that after intravenous infusion of 3 L normal saline and measurement of the tracheal wall changes before and after infusion by scanning with high resolution CT, the pulmonary vasculature of both the individuals with congenital AQP-1 gene deficiency and normal individuals increased in thickness by 20%, but the airway wall of normal individuals increased in thickness by 50% whereas the airway wall of congenital AQP-1 gene-deficient individuals showed no change. These results revealed that AQP-1 has an important role in pulmonary vascular permeability.…”