REGULATION OF EXPRESSION OF HUMAN SP-A1 AND SP-A2 GENES IN FETAL LUNGEXPLANT CULTURE

Human pulmonary surfactant protein A (SP-A) is genetically complex and its regulation may also be complex, reflecting genotypic variability. Fetal lung explants were used to study the regulation of the SP-A gen es, SP-A1 and SP-A2, by dexamethasone, interferon gamma (IFN gamma), c yclic 3',-5' adenosine monophosphate (cAMP), and tumor necrosis factor alpha (TNF alpha). For comparison, the mRNA levels of surfactant prot ein B (SP-B) and its response to test substances were also examined. R esults showed: (a) In control culture total SP-A mRNA varied widely am ong explants (C.V. = 0.70) compared with SP-B (C.V. = 0.26) (b) IFN ga mma significantly increased total SP-A mRNA but there were marked diff erences among fecal lungs in response to all treatments. (c) SP-A1 mRN A concentration is higher than SP-A2 in both control and treated expla nts. (d) SP-A1 alleles are inhibited to a greater degree by dexamethas one than SP-A2 alleles, The relative effect of cAMP and IFN gamma on S P-A1 and SP-A2 mRNA varied widely among explants. We conclude that SP- A genotype may account in part for the marked differences in SP-A mRNA concentration among fetal lungs and that the SP-A genes and/or allele s may be differentially regulated. (C) 1998 Elsevier Science B.V. All rights reserved.