A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps

Am J Respir Cell Mol Biol. 2016 Aug;55(2):170-5. doi: 10.1165/rcmb.2016-0002RC.

Abstract

Animal model systems are invaluable for examining human diseases. Our laboratory recently established a mouse model of nasal polyps (NPs) and investigated similarities and differences between this mouse model and human NPs. We especially focus on the hypothesis that B cell activation occurs during NP generation in the murine model. After induction of ovalbumin-induced allergic rhinosinusitis, 6% ovalbumin and Staphylococcus aureus enterotoxin B (10 ng) were instilled into the nasal cavity of mice three times per week for 8 weeks. The development of structures that somewhat resemble NPs (which we will refer to as NPs) was confirmed by hematoxylin and eosin staining. The mRNA and protein levels of various inflammatory cell markers and mediators were measured by real-time PCR in nasal tissue and by ELISA in nasal lavage fluid (NLF), respectively. Total Ig isotype levels in NLF were also quantitated using the Mouse Ig Isotyping Multiplex kit (EMD Millipore, Billerica, MA) on a Luminex 200 instrument (Life Technologies, Grand Island, NY). Similar to human NPs, there were significant increases in gene expression of inflammatory cell markers, such as CD19, CD138, CD11c, and mast cell protease-6 in nasal tissue samples of the NP group compared with those of the control group. In further investigations of B cell activation, mRNA expressions of B cell activating factor and a proliferation-inducing ligand were found to be significantly increased in mouse NP tissue. B cell-activating factor protein concentration and IgA and IgG1 levels in NLF were significantly higher in the NP group compared with the control group. In this study, the NP mouse model demonstrated enhanced B cell responses, which are reminiscent of B cell responses in human NPs.

Keywords: B cells; animal model; antibodies; chronic rhinosinusitis; nasal polyps.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / metabolism
  • B-Lymphocytes / immunology*
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Immunoglobulin A / metabolism
  • Immunoglobulin G / metabolism
  • Inflammation / pathology
  • Lymphocyte Activation / immunology*
  • Mice, Inbred BALB C
  • Nasal Lavage Fluid
  • Nasal Polyps / genetics
  • Nasal Polyps / immunology*
  • Nasal Polyps / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • B-Cell Activating Factor
  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin G
  • RNA, Messenger
  • Tnfsf13b protein, mouse