Human SP-A protein variants derived from one or both genes stimulate TNF-alpha 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-