Absence of leukotriene B4 receptor 1 confers resistance to airway hyperresponsiveness and Th2-type immune responses.
Bronchial asthma is an increasingly common disorder that remains poorly understood and difficult to manage. The disease is characterized by airway hyperresponsiveness, chronic inflammation, and mucus overproduction. Based on the finding that leukotriene B4 receptor 1 (BLT1) is expressed highly in Th2 lymphocytes, we analyzed the roles of BLT1 using an OVA-induced bronchial asthma model. BLT1-null mice did not develop airway hyperresponsiveness, eosinophilic inflammation, and hyperplasia of goblet cells. Attenuated symptoms were accompanied by reduced IgE production, and accumulation of IL-5 and IL-13 in bronchoalveolar lavage fluid, suggesting attenuated Th2-type immune response in BLT1-null mice. Peribronchial lymph node cells of sensitized BLT1-null mice showed much attenuated proliferation and production of Th2 cytokines upon re-stimulation with Ag in vitro. Thus, LTB4-BLT1 axis is required for the development of Th2-type immune response, and blockade of LTB4 functions through BLT1 would be novel and useful in the effort to ameliorate bronchial asthma and related Th2-biased immune disorders.
Terawaki
Kan
K
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, Japan.
Yokomizo
Takehiko
T
Nagase
Takahide
T
Toda
Akiko
A
Taniguchi
Masahiko
M
Hashizume
Kohei
K
Yagi
Takeshi
T
Shimizu
Takao
T
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000235:genetics* / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D007073:Immunoglobulin E; D009195:Peroxidase; D002118:Calcium