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

Guirong Wang, David S. Phelps, Todd M. Umstead, Joanna Floros

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Abstract

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)-α production by THP-1 cells. We observed that 1) single-gene products and products derived from both genes stimulate TNF-α production, 2) there are differences among SP-A1 and SP-A2 alleles in their ability to stimulate TNF- α production, and 3) the increases in TNF-α 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-Xα 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.

Original languageEnglish (US)
Pages (from-to)L946-L954
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number5 22-5
StatePublished - May 1 2000

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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