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.

Conclusion

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.

Key words: Endostatin, vascular endothelial growth factor, ovalbumin, asthma

Abbreviations used: AHR, Airway hyperresponsiveness, AI, Allergic pulmonary inflammation, BAL, Bronchoalveolar lavage, BALF, Bronchoalveolar lavage fluid, MCP-1, Monocyte chemoattractant protein 1, MIP-1α, Macrophage inflammatory protein 1α, Penh, Enhanced pause, VEGF, Vascular endothelial growth factor, VEGFR, Vascular endothelial growth factor receptor