Endocrinology, Vol 128, 2916-2924, Copyright © 1991 by Endocrine Society

ARTICLES

Differentiation of type II cells during explant culture of human fetal lung is accelerated by endogenous prostanoids and adenosine 3',5'- monophosphate

PL Ballard, LW Gonzales, MC Williams, JM Roberts and MM Jacobs
Department of Pediatrics, University of California, San Francisco 94143.

Explant culture of the fetal lung, in the absence of serum or hormones, results in precocious biochemical and morphological differentiation of alveolar epithelial cells. In this study we tested the hypothesis that these maturational events are induced by endogenous cAMP. During culture of human fetal lung the content of tissue cAMP increased 140% from days 3-6. Treatment with isobutylmethylxanthine caused a further doubling of cAMP content, and indomethacin blocked most of the increase in cAMP. Isobutylmethylxanthine accelerated and indomethacin inhibited the increases during culture in surfactant protein-A (SP-A), SP-A mRNA, SP-B mRNA, phosphatidylcholine content, and activity of fatty acid synthetase. There was no effect of these treatments on the content of SP-C mRNA, which did not increase during culture. Increasing concentrations of prostaglandins E1 and E2 in the presence of indomethacin produced a parallel stimulation of cAMP content, SP-A, and fatty acid synthetase activity. The temporal increase in SP-A was also blocked by inhibitors of protein kinase-A. In morphological studies, indomethacin-treated explants appeared less mature, with decreased intralumenal volume and more columnar epithelial cells. We conclude that increased tissue cAMP levels, stimulated by endogenous prostaglandins, accelerate differentiation of alveolar epithelial cells during explant culture.

This article has been cited by other articles:

				Y. Wang, B. S. Maciejewski, N. Lee, O. Silbert, N. L. McKnight, J. A. Frangos, and J. Sanchez-Esteban Strain-induced fetal type II epithelial cell differentiation is mediated via cAMP-PKA-dependent signaling pathway Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L820 - L827. [Abstract] [Full Text] [PDF]

				A. D. Postle, L. W. Gonzales, W. Bernhard, G. T. Clark, M. H. Godinez, R. I. Godinez, and P. L. Ballard Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells J. Lipid Res., June 1, 2006; 47(6): 1322 - 1331. [Abstract] [Full Text] [PDF]

				L. W. Gonzales, S. H. Guttentag, K. C. Wade, A. D. Postle, and P. L. Ballard Differentiation of human pulmonary type II cells in vitro by glucocorticoid plus cAMP Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L940 - L951. [Abstract] [Full Text] [PDF]

				M. Strayer, R. C. Savani, L. W. Gonzales, A. Zaman, Z. Cui, E. Veszelovszky, E. Wood, Y.-S. Ho, and P. L. Ballard Pre- and Postnatal Lung Development, Maturation, and Plasticity: Human surfactant protein B promoter in transgenic mice: temporal, spatial, and stimulus-responsive regulation Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L394 - L404. [Abstract] [Full Text] [PDF]

				S. Wagle, A. Bui, P. L. Ballard, H. Shuman, J. Gonzales, and L. W. Gonzales Hormonal regulation and cellular localization of fatty acid synthase in human fetal lung Am J Physiol Lung Cell Mol Physiol, August 1, 1999; 277(2): L381 - L390. [Abstract] [Full Text] [PDF]

				M. J. Acarregui, S. T. Penisten, K. L. Goss, K. Ramirez, and J. M. Snyder Vascular Endothelial Growth Factor Gene Expression in Human Fetal Lung In Vitro Am. J. Respir. Cell Mol. Biol., January 1, 1999; 20(1): 14 - 23. [Abstract] [Full Text]

				P. W. Shaul, M. C. Pace, Z. Chen, and T. S. Brannon Developmental Changes in Prostacyclin Synthesis Are Conserved in Cultured Pulmonary Endothelium and Vascular Smooth Muscle Am. J. Respir. Cell Mol. Biol., January 1, 1999; 20(1): 113 - 121. [Abstract] [Full Text]

				L. M. Scavo, R. Ertsey, and B. Q. Gao Human surfactant proteins A1 and A2 are differentially regulated during development and by soluble factors Am J Physiol Lung Cell Mol Physiol, October 1, 1998; 275(4): L653 - L669. [Abstract] [Full Text] [PDF]

				L. M. Scavo, R. Ertsey, C. J. Chapin, L. Allen, and J. A. Kitterman Apoptosis in the Development of Rat and Human Fetal Lungs Am. J. Respir. Cell Mol. Biol., January 1, 1998; 18(1): 21 - 31. [Abstract] [Full Text]

				T. S. Brannon, A. N. MacRitchie, M. A. Jaramillo, T. S. Sherman, I. S. Yuhanna, L. R. Margraf, and P. W. Shaul Ontogeny of cyclooxygenase-1 and cyclooxygenase-2 gene expression in ovine lung Am J Physiol Lung Cell Mol Physiol, January 1, 1998; 274(1): L66 - L71. [Abstract] [Full Text] [PDF]

				J. S. Torday, H. Sun, and J. Qin Prostaglandin E2 integrates the effects of fluid distension and glucocorticoid on lung maturation Am J Physiol Lung Cell Mol Physiol, January 1, 1998; 274(1): L106 - L111. [Abstract] [Full Text] [PDF]

				S. R. Bates, L. W. Gonzales, J.-Q. Tao, P. Rueckert, P. L. Ballard, and A. B. Fisher Recovery of rat type II cell surfactant components during primary cell culture Am J Physiol Lung Cell Mol Physiol, February 1, 2002; 282(2): L267 - L276. [Abstract] [Full Text] [PDF]