Affiliation:
1. Departments of Cellular and Molecular Physiology and
2. Pediatrics, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
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-Agene 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-A1and SP-A2 genes. These data suggest that the SP-A-induced increases in TNF-α 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.
Publisher
American Physiological Society
Subject
Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology
Cited by
104 articles.
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