Leukotriene B4 release from mast cells in IgE-mediated airway hyperresponsiveness and inflammation

Nobuaki Miyahara, Hiroshi Ohnishi, Satoko Miyahara, Katsuyuki Takeda, Shigeki Matsubara, Hiroyuki Matsuda, Masakazu Okamoto, Joan E. Loader, Anthony Joetham, Mitsune Tanimoto, Azzeddine Dakhama, Erwin W. Gelfand

Research output: Contribution to journalArticle

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Abstract

Previous studies have shown that leukotriene B4 (LTB4), a proinflammatory lipid mediator, is linked to the development of airway hyperresponsiveness through the accumulation of IL-13-producing CD8+ T cells, which express a high affinity receptor for LTB4, BLT1 (Miyahara et al., Am J Respir Crit Care Med 2005;172:161-167; J Immunol 2005;174:4979-4984). By using leukotriene A4 hydrolase-deficient (LTA4H-/-) mice, which fail to synthesize LTB4, we determined the role of this lipidmediator in allergen-induced airway responses. Two approaches were used. In the first, LTA4H-/- mice and wild-type (LTA4H+/+) mice were systemically sensitized and challenged via the airways to ovalbumin. In the second, mice were passively sensitized with anti-ovalbumin IgE and exposed to ovalbumin via the airways. Mast cells were generated from bone marrow of LTA4H+/+ mice or LTA4H-/- mice. After active sensitization and challenge, LTA4H-/- mice showed significantly lower airway hyperresponsiveness compared with LTA4H+/+ mice, and eosinophil numbers and IL-13 levels in the bronchoalveoloar lavage of LTA4H-/- mice were also significantly lower. LTA4H-/- mice also showed decreased airway reactivity after passive sensitization and challenge. After LTA4H+/+ mast cell transfer, LTA4H-/- mice showed increased airway reactivity after passive sensitization and challenge, but not after systemic sensitization and challenge. These data confirm the important role for LTB4 in the development of altered airway responses and suggest that LTB4 secretion from mast cells is critical to eliciting increased airway reactivity after passive sensitization with allergen-specific IgE.

Original languageEnglish
Pages (from-to)672-682
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume40
Issue number6
DOIs
Publication statusPublished - Jun 1 2009

Fingerprint

Leukotriene B4
Mast Cells
Immunoglobulin E
Inflammation
Ovalbumin
Interleukin-13
Allergens
Leukotriene B4 Receptors
T-cells
leukotriene A4 hydrolase
Therapeutic Irrigation
Bone
Eosinophils
Lipids
Bone Marrow
T-Lymphocytes

Keywords

  • Cytokines
  • Lipid mediators
  • Lung
  • Rodent
  • T cells

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Leukotriene B4 release from mast cells in IgE-mediated airway hyperresponsiveness and inflammation. / Miyahara, Nobuaki; Ohnishi, Hiroshi; Miyahara, Satoko; Takeda, Katsuyuki; Matsubara, Shigeki; Matsuda, Hiroyuki; Okamoto, Masakazu; Loader, Joan E.; Joetham, Anthony; Tanimoto, Mitsune; Dakhama, Azzeddine; Gelfand, Erwin W.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 40, No. 6, 01.06.2009, p. 672-682.

Research output: Contribution to journalArticle

Miyahara, N, Ohnishi, H, Miyahara, S, Takeda, K, Matsubara, S, Matsuda, H, Okamoto, M, Loader, JE, Joetham, A, Tanimoto, M, Dakhama, A & Gelfand, EW 2009, 'Leukotriene B4 release from mast cells in IgE-mediated airway hyperresponsiveness and inflammation', American Journal of Respiratory Cell and Molecular Biology, vol. 40, no. 6, pp. 672-682. https://doi.org/10.1165/rcmb.2008-0095OC
Miyahara, Nobuaki ; Ohnishi, Hiroshi ; Miyahara, Satoko ; Takeda, Katsuyuki ; Matsubara, Shigeki ; Matsuda, Hiroyuki ; Okamoto, Masakazu ; Loader, Joan E. ; Joetham, Anthony ; Tanimoto, Mitsune ; Dakhama, Azzeddine ; Gelfand, Erwin W. / Leukotriene B4 release from mast cells in IgE-mediated airway hyperresponsiveness and inflammation. In: American Journal of Respiratory Cell and Molecular Biology. 2009 ; Vol. 40, No. 6. pp. 672-682.
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