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

1, 2, 3, 4

  1. Department of Nephrology, Faculty of Medicine, University of Tsukuba, Japan. knagai@md.tsukuba.ac.jp
  2. Department of Life and Environmental System Science Graduate School of Nanobioscience, Yokohama City University, Japan.
  3. Department of Immunology, Faculty of Medicine, University of Tsukuba, Japan.
  4. Department of Nephrology, Faculty of Medicine, University of Tsukuba, Japan.

CER10716 Submission on line
2017 Vol.35, N°5 - PI 0735, PF 0738
Rapid paper

Rheumatology Article

 

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.

PMID: 28850023 [PubMed]

Received: 28/07/2017 - Accepted : 17/08/2017 - In Press: 28/08/2017 - Published: 13/09/2017