Involvement of pentraxin-3 in anti-neutrophil cytoplasmic antibody production induced by aluminum salt adjuvant

Clin Exp Rheumatol. 2017 Sep-Oct;35(5):735-738. Epub 2017 Aug 28.

Abstract

Objectives: Pentraxin 3 (PTX3) is a multifunctional soluble factor. PTX3 can be involved in the regulation of vasculitis and is expressed in the cytoplasm of neutrophils. As anti-neutrophil cytoplasmic antibody (ANCA) is recognised as a cause of vasculitis, we aimed to discover the role of PTX3 in ANCA production in vivo.

Methods: To this end, we used aluminum salt (alum), which induces neutrophil extracellular traps, as an adjuvant for producing anti-myeloperoxidase-ANCA (MPO-ANCA). Specifically, we intraperitoneally injected alum and recombinant MPO (rMPO) into MPO-deficient mice and then measured the concentration of anti-MPO IgG in their blood. To show the involvement of extracellular PTX3 in this model, we assessed PTX3 protein content and host double-stranded DNA levels in the mice's peritoneal fluid after alum injection. In addition, we simultaneously administered recombinant PTX3, rMPO and alum to MPO-deficient mice to assess the function of PTX3 in producing anti-MPO IgG in vivo.

Results: Anti-MPO IgG was produced by the alum + rMPO immunisation model in MPO-deficient but not wildtype mice. Injection of alum induced extracellular PTX3 as well as double-stranded DNA and dead cells in MPO-deficient mice. Simultaneous injection of recombinant PTX3 with rMPO and alum attenuated the production of anti-MPO IgG in MPO-deficient mice.

Conclusions: Our current findings provide evidence that PTX3 attenuates the production of murine MPO-ANCA.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Alum Compounds / pharmacology*
  • Animals
  • Antibodies, Antineutrophil Cytoplasmic / blood*
  • Ascitic Fluid / immunology
  • Ascitic Fluid / metabolism
  • C-Reactive Protein / administration & dosage
  • C-Reactive Protein / immunology*
  • C-Reactive Protein / metabolism
  • DNA / immunology
  • DNA / metabolism
  • Extracellular Traps / immunology
  • Extracellular Traps / metabolism
  • Female
  • Immunoglobulin G / blood*
  • Male
  • Metabolism, Inborn Errors / blood
  • Metabolism, Inborn Errors / enzymology
  • Metabolism, Inborn Errors / immunology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / administration & dosage
  • Nerve Tissue Proteins / immunology*
  • Nerve Tissue Proteins / metabolism
  • Peroxidase / administration & dosage
  • Peroxidase / deficiency
  • Peroxidase / genetics
  • Peroxidase / immunology*

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Antibodies, Antineutrophil Cytoplasmic
  • Immunoglobulin G
  • Nerve Tissue Proteins
  • neuronal pentraxin
  • aluminum sulfate
  • C-Reactive Protein
  • DNA
  • Peroxidase

Supplementary concepts

  • Myeloperoxidase Deficiency