Interleukin-33 and alveolar macrophages contribute to the mechanisms underlying the exacerbation of IgE-mediated airway inflammation and remodelling in mice

Immunology. 2013 Jun;139(2):205-18. doi: 10.1111/imm.12071.

Abstract

Allergen-specific IgE has long been regarded as a major molecular component of allergic asthma. Additionally, there is increasing evidence of the important roles of interleukin-33 (IL-33) in the disease. Here, we show that IL-33 and alveolar macrophages play essential roles in the exacerbation of IgE-mediated airway inflammation and remodelling. BALB/c mice passively sensitized with ovalbumin (OVA)-specific IgE monoclonal antibody (mAb) were challenged with OVA seven times intratracheally. The seventh challenge exacerbated airway inflammation and remodelling compared with the fourth challenge; furthermore, markedly increased expression of IL-33 in the lungs was observed at the fourth and seventh challenges. When anti-IL-33 or anti-ST2 antibody was administered during the fourth to seventh challenge, airway inflammation and remodelling were significantly inhibited at the seventh challenge. Because increases of IL-33(+) and ST2(+) alveolar macrophages and ST2(+) CD4(+) T cells in the lungs were observed at the fourth challenge, the roles of macrophages and CD4(+) cells were investigated. Depletion of macrophages by 2-chloroadenosine during the fourth to seventh challenge suppressed airway inflammation and remodelling, and IL-33 production in the lung at the seventh challenge; additionally, anti-CD4 mAb inhibited airway inflammation, but not airway remodelling and IL-33 production. Meanwhile, treatment with 2-chloroadenosine or anti-CD4 mAb decreased IL-33-induced airway inflammation in normal mice; airway remodelling was repressed only by 2-chloroadenosine. These results illustrate that macrophage-derived IL-33 contributes to the exacerbation of IgE-mediated airway inflammation by mechanisms associated with macrophages and CD4(+) cells, and airway remodelling through the activation of macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Chloroadenosine / immunology
  • 2-Chloroadenosine / pharmacology
  • Airway Remodeling / drug effects
  • Airway Remodeling / immunology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Asthma / immunology
  • Asthma / metabolism
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Flow Cytometry
  • Immunoglobulin E / immunology*
  • Immunohistochemistry
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Interleukins / pharmacology
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin / metabolism
  • Respiratory System / immunology
  • Respiratory System / metabolism
  • Respiratory System / pathology

Substances

  • Antibodies, Monoclonal
  • CD4 Antigens
  • Il1rl1 protein, mouse
  • Il33 protein, mouse
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Receptors, Interleukin
  • 2-Chloroadenosine
  • Immunoglobulin E
  • Ovalbumin