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production in the THP-1 cell line
Departments of 1 Cellular and Molecular Physiology and 2 Pediatrics, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
In humans, two functional genes of
surfactant protein (SP) A, SP-A1 and
SP-A2, and several alleles of each functional gene have been characterized. SP-A is a multimeric molecule consisting of
six trimers. Each trimer contains two SP-A1 molecules and one SP-A2
molecule. Until now, it has been unclear whether a single SP-A
gene product is functional or whether there are functional differences
either among alleles or between single-gene SP-A products and SP-A
products derived from both genes. We tested the ability of in vitro
expressed SP-A variants to stimulate tumor necrosis factor (TNF)-
production by THP-1 cells. We observed that 1) single-gene
products and products derived from both genes stimulate TNF-
production, 2) there are differences among SP-A1 and
SP-A2 alleles in their ability to stimulate TNF- production,
and 3) the increases in TNF- production are lower after
treatment with the SP-A1 alleles than after treatment with the
SP-A2 alleles. Furthermore, coexpressed SP-As from
SP-A1 and SP-A2 genes have a higher activity compared
with SP-As from individual alleles or mixed SP-As from SP-A1
and SP-A2 genes. These data suggest that the SP-A-induced
increases in TNF- levels differ among SP-A variants and appear to be
affected by SP-A genotype and whether SP-A is derived from one or both genes.
allele; macrophage; surfactant protein A; tumor necrosis factor-
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