Pulmonary dysfunction in neonatal SP-B-deficient mice

Tokieda, Keisuke; Whitsett, Jeffrey A.; Clark, Jean C.; Weaver, Timothy E.; Ikeda, Kazushige; McConnell, Keith; Jobe, Alan H.; Ikegami, Machiko; Iwamoto, Harriet S.

doi:10.1152/ajplung.1997.273.4.l875

Cited by 93 publications

(89 citation statements)

References 22 publications

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“…The high surface and physiological activity of SP-B vs. SP-C is consistent with the lethal nature of congenital SP-B deficiency in humans (14,19,31,32). Lethal respiratory failure also occurs in "knockout" mice lacking the SP-B gene (9), and compliance abnormalities exist even in mice that are SP-B (ϩ/Ϫ) heterozygotes (8,50).…”

Section: Discussionsupporting

confidence: 57%

Content-dependent activity of lung surfactant protein B in mixtures with lipids

Wang

Baatz

Holm

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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The content-dependent activity of surfactant protein (SP)-B was studied in mixtures with dipalmitoyl phosphatidylcholine (DPPC), synthetic lipids (SL), and purified phospholipids (PPL) from calf lung surfactant extract (CLSE). At fixed SP-B content, adsorption and dynamic surface tension lowering were ordered as PPL/SP-B ≈ SL/SP-B > DPPC/SP-B. All mixtures were similar in having increased surface activity as SP-B content was incrementally raised from 0.05 to 0.75% by weight. SP-B had small but measurable effects on interfacial properties even at very low levels ≤0.1% by weight. PPL/SP-B (0.75%) had the highest adsorption and dynamic surface activity, approaching the behavior of CLSE. All mixtures containing 0.75% SP-B reached minimum surface tensions <1 mN/m in pulsating bubble studies at low phospholipid concentration (1 mg/ml). Mixtures of PPL or SL with SP-B (0.5%) also had minimum surface tensions <1 mN/m at 1 mg/ml, whereas DPPC/SP-B (0.5%) reached <1 mN/m at 2.5 mg/ml. Physiological activity also was strongly dependent on SP-B content. The ability of instilled SL/SP-B mixtures to improve surfactant-deficient pressure-volume mechanics in excised lavaged rat lungs increased as SP-B content was raised from 0.1 to 0.75% by weight. This study emphasizes the crucial functional activity of SP-B in lung surfactants. Significant differences in SP-B content between exogenous surfactants used to treat respiratory disease could be associated with substantial activity variations.

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Section: Discussionsupporting

confidence: 57%

Content-dependent activity of lung surfactant protein B in mixtures with lipids

Wang

Baatz

Holm

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The hydrophobic surfactant protein SP-B has been known to play a critical role in lung function. This was evidenced by studies in which the removal of SP-B via genetic mutation in mice resulted in RDS-like symptoms in neonates [15,16].…”

Section: Pulmonary Surfactant Functionalitymentioning

confidence: 99%

Equation of state for a coarse-grained DPPC monolayer at the air/water interface

Adhangale

Gaver

2006

Molecular Physics

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Pulmonary surfactant, a complex mixture of phospholipids and proteins, secreted by the type II epithelial cells in the lungs, is crucial to reducing the effort required for breathing. A lack of adequate amounts of pulmonary surfactant in underdeveloped lungs of premature infants results in infant respiratory distress syndrome (RDS). Surfactant replacement therapy (SRT) is the approved method of mitigating the effects of RDS. The development of new SRT regimens requires a fundamental understanding of the links between surfactant biochemistry and functionality. We use a coarse-grained (CG) model to predict the surface pressure-surface concentration relationship (equation of state) for pure DPPC, which is a major component of endogenous and synthetic pulmonary surfactant mixtures. We show that the model can be efficiently used to predict the equation of state in excellent agreement with experimental results. We also study the structure of the monolayer as a function of the surface tension of the system. We show that a decrease in the applied surface tension results in an increase in order in the head group region and a decrease in order in the tail region of DPPC. This technique may be useful in the prediction of equations of state for surfactant replacements.

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“…SP-B is a 79-aa polypeptide expressed in alveolar type II cells that interacts with phospholipids to enhance the surface tension of the alveolus in the lung (24). Deficiency in SP-B has been shown to affect lung function, and results in reduced lung compliance (25). SP-B concentrations were analyzed from total lung homogenates and bronchoalveolar lavages from …”

Section: Surfactant Protein-b (Sp-b)mentioning

confidence: 99%

Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

Krane

Fortner

Hand

et al. 2001

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

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106

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Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveolar type II cells, and in tracheal and bronchial epithelium. Aqp5 knockout (Aqp5 ؊/؊ ) mice were used to analyze AQP5 function in pulmonary physiology. Compared with Aqp5 ؉/؉ mice, Aqp5 ؊/؊ mice show a significantly increased concentration-dependent bronchoconstriction to intravenously administered Ach, as shown by an increase in total lung resistance and a decrease in dynamic lung compliance (P < 0.05). Likewise, Penh, a measure of bronchoconstriction, was significantly enhanced in Aqp5 ؊/؊ mice challenged with aerosolized methacholine (P < 0.05). The hyperreactivity to bronchoconstriction observed in the Aqp5 ؊/؊ mice was not due to differences in tracheal smooth muscle contractility in isolated preparations or to altered levels of surfactant protein B. These data suggest a novel pathway by which AQP5 influences bronchoconstriction. This observation is of special interest because studies to identify genetic loci involved in airway hyperresponsiveness associated with asthma bracket genetic intervals on human chromosome 12q and mouse chromosome 15, which contain the Aqp5 gene.A quaporin 5 (AQP5) is a mercury-sensitive water channel expressed in mouse salivary gland acinar cells, alveolar type I cells, lacrimal glands, and the eye (1-3). However, the function of AQP5 in mouse lung physiology and pathophysiology is largely unknown. Recent studies have explored the regulation of Aqp5 gene expression in normal and disease states. In a mouse model of acute lung injury, AQP5 mRNA and protein expression were significantly decreased in association with pulmonary inflammation and edema resulting from adenoviral infection (4). Moreover, AQP5 expression in a murine lung epithelial cell line (MLE-12) is modulated by the proinf lammatory cytokine TNF-␣ through an nuclear factor (NF)-B-dependent pathway (5). Keratinocyte growth factor also has been shown to mediate the differentiation status of alveolar epithelial cells and AQP5 expression (6). However, a clear understanding of AQP5 function in the lung remains to be discerned.Previously published studies have addressed functional questions limited to the examination of the role of AQP5 in type I cells in fluid clearance and airspace-capillary osmotic water permeability. Of significance, isolated perfused lungs from Aqp5 Ϫ/Ϫ mice were shown to have a 10-fold reduction in airspace-capillary osmotic water permeability (7). Experiments addressing the role of AQP5 in alveolar fluid clearance failed to indicate a role for AQP5 in this process under certain physiological conditions (8). Based on the results of these studies, some have concluded that AQP5 does not play a major role in lung physiology. Contrary to these conclusions, the data reported here clearly define a...

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Pulmonary dysfunction in neonatal SP-B-deficient mice

Cited by 93 publications

References 22 publications

Content-dependent activity of lung surfactant protein B in mixtures with lipids

Content-dependent activity of lung surfactant protein B in mixtures with lipids

Equation of state for a coarse-grained DPPC monolayer at the air/water interface

Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

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