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Am J Physiol Lung Cell Mol Physiol 275: L653-L669, 1998;
1040-0605/98 $5.00
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Vol. 275, Issue 4, L653-L669, October 1998

Human surfactant proteins A1 and A2 are differentially regulated during development and by soluble factors

Louis M. Scavo, Robert Ertsey, and Bi Qi Gao

Cardiovascular Research Institute and Department of Pediatrics, University of California, San Francisco, California 94143-9972

An RT-PCR method for the relative quantitation of the mRNAs for human surfactant protein (SP) A1 and SP-A2 was developed, verified, and then utilized to determine the relative levels of these mRNAs in fetal and adult lung samples in vivo, as well as in cultured human fetal lung explants and H441 cells. For the cultured tissue and cells, we assessed the effects of a variety of soluble factors known to modulate total SP-A. Comprehensive analysis revealed many significant findings, including the following: both mRNAs were expressed as early as 15 wk of gestation; throughout midgestation, SP-A1 was present at higher levels than SP-A2, with an average ratio of 30:1. In the adult lung, SP-A1 mRNA was present at lower levels than SP-A2, with a ratio of 0.4:1, whereas in H441 cells, the ratio was 0.85:1. In fetal lung cultured for 4 days, both mRNAs increased, with a greater increase in SP-A2 (97-fold) than in SP-A1 (15-fold), resulting in a final ratio of 4:1. Differential regulation was demonstrated for 8-(4-chlorophenylthio)-cAMP, interferon (IFN)-gamma , tumor necrosis factor-alpha , and transforming growth factor (TGF)-beta in the human fetal lung explant system, with SP-A2 being more affected, and for IFN-gamma and TGF-beta in the H441 cells, where SP-A1 showed greater regulation. Of the soluble factors tested, IFN-gamma and TGF-beta had the most potent and consistent effects in both systems.

human fetal lung; H441 cells; reverse transcription-polymerase chain reaction; interferon-gamma ; tumor necrosis factor-alpha ; transforming growth factor-beta ; adenosine 3',5'-cyclic monophosphate; dexamethasone


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