Human SP-A protein variants derived from one or both genes stimulate TNF-alpha production in the THP-1 cell line

In humans, two functional genes of surfactant protein (SP) A, SP-AI 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 func tional differences either among alleles or between single-gene SP-A product s and SP-A products derived from both genes. We tested the ability of in vi tro expressed SP-A variants to stimulate tumor necrosis factor (TNF)-alpha production by THP-1 cells. We observed that I) single-gene products and pro ducts derived from both genes stimulate TNF-alpha production, 2) there are differences among SP-AI and SP-A2 alleles in their ability to stimulate TNF -alpha production, and 3) the increases in TNF-alpha production are lower a fter treatment with the SP-AI alleles than after treatment with the SP-A2 a lleles. Furthermore, coexpressed SP-As from SP-AI and SP-A2 genes have a hi gher activity compared with SP-As from individual alleles or mixed SP-As fr om SP-A1 and SP-A2 genes. These data suggest that the SP-A-induced increase s in TNF-alpha levels differ among SP-A variants and appear to be affected by SP-A genotype and whether SP-Ais derived from one or both genes.