Abstract
Pulmonary developmental alveologenesis occurs, in substantial part, by subdivision (septation) of the gas-exchange saccules of the morphologically immature lung. It determines the starting point of age- and disease-related alveolar loss. Because alveologenesis requires additional cell membranes, we previously asked whether apoE, which delivers lipids to cells, affects pulmonary alveologenesis; male apoE−/− mice had impaired alveologenesis. We now report that, in contrast to male apoE−/− mice, female apoE−/− mice had full developmental alveologenesis. Among mice null for LDL receptor (Ldlr−/−), the receptor for apoE, females had full alveologenesis; by contrast, Ldlr−/− males, as previously shown for apoE−/− males, had impaired alveologenesis. Thus, the absence of apoE and its receptor, Ldlr, results in impaired developmental alveologenesis in males, but their absence does not impair architectural developmental alveologenesis in females. We conclude 1) regulation of alveologenesis is a new function for apoE and Ldlr, 2) one expressed in a sexually dimorphic manner, and 3) females have different molecular requirements for alveologenesis than males, which protects them from its impairment by the absence of apoE and its receptor.
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Abbreviations
- Ldlr:
-
LDL receptor
- L m :
-
distance between alveolar walls
- N a :
-
number of alveoli
- S a :
-
surface area
- S/V :
-
surface to volume ratio
- V a :
-
volume of an average alveolus
- V v :
-
volume density or volume fraction
References
Massaro GD, Massaro D 1996 Formation of pulmonary alveoli and gas-exchange surface area: quantitation and regulation. Annu Rev Physiol 58: 73–92
Tenney SM, Remmers JE 1963 Comparative quantitative morphology of mammalian lung: diffusing area. Nature 197: 54–56
Angus GE, Thurlbeck WE 1972 Number of alveoli in human lung. J Appl Physiol 32: 483–485
Neas LM, Schwartz J 1996 The determinants of pulmonary diffusing capacity in a national sample of U.S. adults. Am J Respir Crit Care Med 153: 656–664
Massaro D, Massaro GD 2008 Apoetm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function. Am J Physiol Lung Cell Mol Physiol 294: L991–L997
Massaro D, Massaro GD 2006 Estrogen receptor regulation of pulmonary alveolar dimensions: alveolar sexual dimorphism in mice. Am J Physiol Lung Cell Mol Physiol 290: L866–L870
Scherle W 1970 A simple method for volumetry of organs in quantitative stereology. Mikroskopie 26: 57–60
Massaro GD, Massaro D 1996 Postnatal treatment with retinoic acid increases the number of alveoli in rats. Am J Physiol 270: L305–L310
Massaro GD, Massaro D 1997 Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Nat Med 3: 675–677
Cruz-Orive LM 1987 Particle number can be estimated using a disector of unknown thickness: the selector. J Microsc 145: 121–142
Massaro GD, Mortola JP, Massaro D 1995 Sexual dimorphism in the architecture of the lung's gas-exchange region. Proc Natl Acad Sci USA 92: 1105–1107
Massaro D, Clerch LB, Massaro GD 2007 Estrogen receptor-alpha regulates pulmonary alveolar loss and regeneration in female mice: morphometric and gene expression studies. Am J Physiol Lung Cell Mol Physiol 293: L222–L228
Massaro GD, Mortola JP, Massaro D 1996 Estrogen modulates the dimensions of the lung's gas-exchange surface area and alveoli in female rats. Am J Physiol 270: L110–L114
Acknowledgements
We thank Helene Hadden, M.D., Ph.D., for critically reading an early version of the manuscript and for helpful suggestions and Ms. Zofia Opalka for expert technical assistance.
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Supported by NHLBI grant 020366-35.The authors report no conflicts of interest.
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Massaro, D., Massaro, G. Developmental Alveologenesis: New Roles for ApoE and LDL Receptor. Pediatr Res 70, 458–461 (2011). https://doi.org/10.1203/PDR.0b013e31822f24df
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DOI: https://doi.org/10.1203/PDR.0b013e31822f24df
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