Requirement for leukotriene B4 receptor 1 in allergen-induced airway hyperresponsiveness.
BACKGROUND
Leukotriene B4 (LTB4) is a rapidly synthesized, early leukocyte chemoattractant that signals via its cell surface receptor, leukotriene B4 receptor 1 (BLT1), to attract and activate leukocytes during inflammation. A role for the LTB4-BLT1 pathway in allergen-induced airway hyperresponsiveness and inflammation is not well defined.


OBJECTIVE
To define the role of the LTB4 receptor (BLT1) in the development of airway inflammation and altered airway function.


METHODS
BLT1-deficient (BLT1 -/-) mice and wild-type mice were sensitized to ovalbumin by intraperitoneal injection and then challenged with ovalbumin via the airways. Airway responsiveness to inhaled methacholine, bronchoalveolar lavage fluid cell composition and cytokine levels, and lung inflammation and goblet cell hyperplasia were assessed.


RESULTS
Compared with wild-type mice, BLT1 -/- mice developed significantly lower airway responsiveness to inhaled methacholine, lower goblet cell hyperplasia in the airways, and decreased interleukin (IL)-13 production both in vivo, in the bronchoalveolar lavage fluid, and in vitro, after antigen stimulation of lung cells in culture. Intracellular cytokine staining of lung cells revealed that bronchoalveolar lavage IL-13 levels and numbers of IL-13(+)/CD4+ and IL-13(+)/CD8+ T cells were also reduced in BLT1 -/- mice. Reconstitution of sensitized and challenged BLT1 -/- mice with allergen-sensitized BLT1 +/+ T cells fully restored the development of airway hyperresponsiveness. In contrast, transfer of naive T cells failed to do so.


CONCLUSIONS
These data suggest that BLT1 expression on primed T cells is required for the full development of airway hyperresponsiveness, which appears to be associated with IL-13 production in these cells.
Miyahara
Nobuaki
N
National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
Takeda
Katsuyuki
K
Miyahara
Satoko
S
Matsubara
Shigeki
S
Koya
Toshiyuki
T
Joetham
Anthony
A
Krishnan
Elangovan
E
Dakhama
Azzeddine
A
Haribabu
Bodduluri
B
Gelfand
Erwin W
EW
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001991:Bronchitis / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D005260:Female; D018793:Interleukin-13 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018102:Receptors, Leukotriene B4 / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D000485:Allergens; D017252:CD3 Complex; D016207:Cytokines; D018793:Interleukin-13; D018102:Receptors, Leukotriene B4; D010047:Ovalbumin