Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice

Int Immunol. 2015 Sep;27(9):459-66. doi: 10.1093/intimm/dxv014. Epub 2015 Apr 7.

Abstract

Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing factor in developing sensory neurons, is now recognized as a key player in immune, cardiovascular, bone metabolism and neurological systems. Here we established an anti-Sema3A monoclonal antibody that neutralizes the effects of Sema3A both in vitro and in vivo. The anti-Sema3A neutralization chick IgM antibodies were screened by combining an autonomously diversifying library selection system and an in vitro growth cone collapse assay. We further developed function-blocking chick-mouse chimeric and humanized anti-Sema3A antibodies. We found that our anti-Sema3A antibodies were effective for improving the survival rate in lipopolysaccharide-induced sepsis in mice. Our antibody is a potential therapeutic agent that may prevent the onset of or alleviate symptoms of human diseases associated with Sema3A.

Keywords: antibody therapy; function-blocking antibody; mice; semaphorin; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology*
  • COS Cells
  • Cell Line
  • Chickens
  • Chlorocebus aethiops
  • Humans
  • Lipopolysaccharides / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Proteins / immunology
  • Semaphorin-3A / immunology*
  • Sepsis / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Lipopolysaccharides
  • Recombinant Proteins
  • Semaphorin-3A