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Matsumoto T, Matsushima Y, Toda M, et al. Activated protein C modulates the proinflammatory activity of dendritic cells. J Asthma Allergy. 2015;8:29-37doi: 10.2147/JAA.S75261.
Matsumoto, T., Matsushima, Y., Toda, M., Roeen, Z., D'Alessandro-Gabazza, C. N., Hinneh, J. A., Harada, E., Yasuma, T., Yano, Y., Urawa, M., Kobayashi, T., Taguchi, O., & Gabazza, E. C. (2015). Activated protein C modulates the proinflammatory activity of dendritic cells. Journal of asthma and allergy, 829-37. https://doi.org/10.2147/JAA.S75261
Matsumoto, Takahiro, et al. "Activated protein C modulates the proinflammatory activity of dendritic cells." Journal of asthma and allergy vol. 8 (2015): 29-37. doi: https://doi.org/10.2147/JAA.S75261
Matsumoto T, Matsushima Y, Toda M, Roeen Z, D'Alessandro-Gabazza CN, Hinneh JA, Harada E, Yasuma T, Yano Y, Urawa M, Kobayashi T, Taguchi O, Gabazza EC. Activated protein C modulates the proinflammatory activity of dendritic cells. J Asthma Allergy. 2015 May 07;8:29-37. doi: 10.2147/JAA.S75261. eCollection 2015. PMID: 26005353; PMCID: PMC4428377.
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J Asthma Allergy. 2015 May 07;8:29-37. doi: 10.2147/JAA.S75261. eCollection 2015.

Activated protein C modulates the proinflammatory activity of dendritic cells.

Journal of asthma and allergy

Takahiro Matsumoto, Yuki Matsushima, Masaaki Toda, Ziaurahman Roeen, Corina N D'Alessandro-Gabazza, Josephine A Hinneh, Etsuko Harada, Taro Yasuma, Yutaka Yano, Masahito Urawa, Tetsu Kobayashi, Osamu Taguchi, Esteban C Gabazza

Affiliations

  1. Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan ; BONAC Corporation, BIO Factory 4F, Fukuoka, Japan.
  2. Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
  3. Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan ; Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
  4. Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan ; Iwade Research Institute of Mycology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
  5. Department of Endocrinology, Diabetes and Metabolism, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
  6. Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.

PMID: 26005353 PMCID: PMC4428377 DOI: 10.2147/JAA.S75261

Abstract

BACKGROUND: Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells.

MATERIALS AND METHODS: Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells.

RESULTS: Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C-treated ovalbumin-pulsed dendritic cells had significantly less airway hyperresponsiveness, significantly decreased lung concentrations of Th1 and Th2 cytokines, and less plasma concentration of immunoglobulin E when compared to control mice.

CONCLUSION: These results suggest that dendritic cells mediate the immunosuppressive effect of activated protein C during allergic inflammation.

Keywords: allergy; coagulation; dendritic cells; protein C pathway

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