Intrinsic AHR in IL-5 transgenic mice is dependent on CD4(+) cells and CD49d-mediated signaling.
Overexpression of interleukin (IL)-5 by the airway epithelium in mice using the rat CC10 promoter (NJ.1726 line) leads to several histopathologies characteristic of human asthma, including airway hyperreactivity (AHR). We investigated the contribution of B and T cells, as well as CD4 expression, to the development of AHR in IL-5 transgenic mice. NJ.1726 mice on a T cell or CD4 knockout background, but not on a B cell knockout background, lost intrinsic AHR. These effects occurred without decreases in IL-5 or eosinophils. We further investigated the contribution of alpha(4)-integrin signaling to the development of AHR in IL-5 transgenic mice through the administration of anti-CD49d (alpha(4)-integrin) antibody (PS/2). Administration of PS/2 resulted in immediate (16-h) inhibition of AHR. The inhibition of AHR was not associated with a decrease in airway eosinophils. These studies demonstrate that, despite the presence of increased levels of IL-5 and eosinophils in the lungs of NJ.1726 mice, CD4(+) cells and alpha(4)-integrin signaling are necessary for the intrinsic AHR that develops in IL-5 transgenic mice.
Borchers
M T
MT
Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259, USA.
Crosby
J
J
Justice
P
P
Farmer
S
S
Hines
E
E
Lee
J J
JJ
Lee
N A
NA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology; D001980:Bronchi / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D004802:Eosinophilia / Q000473:pathology; D039441:Integrin alpha4; D015848:Interleukin-5 / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000166:cytology; D008171:Lung Diseases / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*
D000906:Antibodies; D015703:Antigens, CD; D015848:Interleukin-5; D039441:Integrin alpha4