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

Published on Jun 1, 2009in American Journal of Respiratory Cell and Molecular Biology5.373
· DOI :10.1165/RCMB.2008-0095OC
Nobuaki Miyahara33
Estimated H-index: 33
Hiroshi Ohnishi20
Estimated H-index: 20
(University of Colorado Denver)
+ 9 AuthorsErwin W. Gelfand113
Estimated H-index: 113
(University of Colorado Denver)
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 lipid mediator 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...
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