A potent antiangiogenic factor, endostatin prevents the development of asthma in a murine model.
BACKGROUND
Clinical studies suggest a role for angiogenesis in the development and persistence of chronic asthma, but whether angiogenic mediators contribute to acute asthma has not been fully studied.


OBJECTIVE
The aim of this study was to investigate a role of vascular endothelial growth factor (VEGF), a major angiogenic and proinflammatory mediator, in allergen-induced acute asthma and to determine whether endostatin/Fc, a potent antiangiogenic factor can attenuate allergic airway responses.


METHODS
We sensitized BALB/c mice with ovalbumin. We measured serum VEGF and examined immunoreactive VEGF around the airways 48 hours after the last challenge with either aerosolized PBS or ovalbumin once per day for 3 days. We also treated ovalbumin-sensitized mice with either endostatin/Fc or control fusion protein at the time of challenge with ovalbumin. We analyzed allergic airway responses 48 hours after the last ovalbumin challenge.


RESULTS
Ovalbumin challenge induced immunolocalization of numerous VEGF-positive cells around airways and increased serum VEGF levels. Treatment with endostatin/Fc inhibited the airway hyperresponsiveness, pulmonary allergic inflammation, production of ovalbumin-specific IgE, and lung inflammatory mediators. Both VEGF-dependent and independent mechanisms are indicated by results using antibody blockade of VEGF receptors, which caused decreased allergic pulmonary inflammation but did not alter airway hyperresponsiveness or serum IgE levels.


CONCLUSIONS
These data demonstrate for the first time that recombinant endostatin can prevent the development of asthma features in a mouse model and suggest that this class of agents merits further study as novel therapeutics for asthma.
Suzaki
Yasue
Y
Second Department of Internal Medicine, Nara Medical University, Nara, Tokyo.
Hamada
Kaoru
K
Sho
Masayuki
M
Ito
Toshihiro
T
Miyamoto
Kenichi
K
Akashi
Satoru
S
Kashizuka
Hisanori
H
Ikeda
Naoya
N
Nakajima
Yoshiyuki
Y
Iwase
Michiko
M
Homma
Ikuo
I
Kobzik
Lester
L
Kimura
Hiroshi
H
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D043169:Endostatins / Q000627:therapeutic use*; D005260:Female; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000502:physiology
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A