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-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)-alpha production by THP-1 cells. We observed that 1) single-gene products and products derived from both genes stimulate TNF-alpha production, 2) there are differences among SP-A1 and SP-A2 alleles in their ability to stimulate TNF-alpha production, and 3) the increases in TNF-alpha 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-alpha 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.
Wang
G
G
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Phelps
D S
DS
Umstead
T M
TM
Floros
J
J
D000483:Alleles; D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002460:Cell Line; D018076:DNA, Complementary; D018628:Gene Dosage; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D006801:Humans; D008168:Lung / Q000166:cytology*; D016676:Macrophages, Alveolar / Q000502:physiology*; D011510:Proteolipids / Q000737:chemistry / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000235:genetics*; D018411:Spodoptera; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D018076:DNA, Complementary; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human; D014409:Tumor Necrosis Factor-alpha