AJP - Lung Cellular and Molecular Physiology, Vol 264, Issue 5 465-L474, Copyright © 1993 by American Physiological Society

ARTICLES

Oxygen modulates the differentiation of human fetal lung in vitro and its responsiveness to cAMP

M. J. Acarregui, J. M. Snyder and C. R. Mendelson
Department of Biochemistry, Cecil H. & Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235-9038.

Previously, it was found that lung explants from mid-trimester human abortuses differentiate spontaneously in organ culture in serum-free defined medium in an atmosphere of 95% air-5% CO2. Dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) treatment of human fetal lung in culture increases the rate of morphological differentiation and enhances expression of the surfactant protein A (SP-A) gene. To begin to define the factors responsible for this accelerated in vitro differentiation, we analyzed the effects of atmospheric oxygen on the morphological and biochemical development of human fetal lung in culture and on responsiveness of the cultured tissue to DBcAMP. We found that when lung explants were maintained in an atmosphere containing 1% oxygen they failed to differentiate spontaneously and no induction of SP-A gene expression was apparent. Furthermore, at 1% oxygen, DBcAMP had no effect to stimulate morphological differentiation or SP-A gene expression. When lung tissues that had been maintained for 5 days in 1% oxygen were transferred to an environment containing 20% oxygen, there was rapid morphological development and induction of SP-A gene expression. The effects on morphological development were manifest within 24 h of transfer to the 20% oxygen environment; within 72 h, a marked stimulatory effect of DBcAMP on SP-A gene expression also was observed. Our findings further suggest that the effects of oxygen on the levels of SP-A and SP-A mRNA are concentration dependent. Interestingly, the inductive effects of DBcAMP on SP-A gene expression were apparent only at oxygen concentrations > or = 10%. Morphological differentiation of the cultured human fetal lung tissue also was influenced by oxygen in a concentration-dependent manner. These findings suggest that oxygen plays an important permissive role in the spontaneous differentiation of human fetal lung in vitro.

This article has been cited by other articles:

				D. Liu, M. Yi, M. Smith, and C. R. Mendelson TTF-1 response element is critical for temporal and spatial regulation and necessary for hormonal regulation of human surfactant protein-A2 promoter activity Am J Physiol Lung Cell Mol Physiol, August 1, 2008; 295(2): L264 - L271. [Abstract] [Full Text] [PDF]

				Q. Zhang, O. W. Moe, J. A. Garcia, and C. C. W. Hsia Regulated expression of hypoxia-inducible factors during postnatal and postpneumonectomy lung growth Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L880 - L889. [Abstract] [Full Text] [PDF]

				M. van Tuyl, J. Liu, J. Wang, M. Kuliszewski, D. Tibboel, and M. Post Role of oxygen and vascular development in epithelial branching morphogenesis of the developing mouse lung Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L167 - L178. [Abstract] [Full Text] [PDF]

				K. R. KHUBCHANDANI and J. M. SNYDER Surfactant protein A (SP-A): the alveolus and beyond FASEB J, January 1, 2001; 15(1): 59 - 69. [Abstract] [Full Text] [PDF]

				J. J. E. Haddad and S. C. Land O2-evoked regulation of HIF-1alpha and NF-kappa B in perinatal lung epithelium requires glutathione biosynthesis Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L492 - L503. [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]

				J. L. Alcorn, M. E. Smith, J. F. Smith, L. R. Margraf, and C. R. Mendelson Primary Cell Culture of Human Type II Pneumonocytes: Maintenance of a Differentiated Phenotype and Transfection with Recombinant Adenoviruses Am. J. Respir. Cell Mol. Biol., December 1, 1997; 17(6): 672 - 682. [Abstract] [Full Text]

				M. Yi, G.-X. Tong, B. Murry, and C. R. Mendelson Role of CBP/p300 and SRC-1 in Transcriptional Regulation of the Pulmonary Surfactant Protein-A (SP-A) Gene by Thyroid Transcription Factor-1 (TTF-1) J. Biol. Chem., January 18, 2002; 277(4): 2997 - 3005. [Abstract] [Full Text] [PDF]