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Angiogenesis in response to allergen challenge in a murine model of asthma
S190 Abstracts
Angiogenesis in Response to Allergen Challenge in a Murine Model of Asthma S. S. Aceves, S. Y. Lee, J. Y. Cho, D. H. Broide; Division of Allergy, Immunology, University of California, San Diego, La Jolla, CA. RATIONALE: Airways of patients with fatal asthma are edematous and contain increased vasculature. Recent reports have demonstrated that there is increased expression of proangiogenic cytokines in patients with untreated asthma as well as increased expression of anti-angiogenic molecules in patients who have controlled asthma. METHODS: Using a murine model of ova induced asthma in which mice are exposed to repetitive ova challenge for 1–3 months, we have studied the extent of angiogenesis as well as the expression levels of various molecules and growth factors involved in vasculogenesis in response to allergen challenge. RESULTS: Following ova challenge, there is a significant increase in the vascularity in the lungs of ova challenged compared to non-ova challenged mice as assessed by image analysis (0.30 ± 0.07 vs. 0.04 ± 0.02) (p=0.05). The increase in lung vascularity following repetitive ova challenge is associated with increased levels of expression of the angiogenic growth factor VEGF in BAL fluid from ova challenged mice compared to non-ova challenged mice as assessed by ELISA (p=0.05). In addition, we show a 5-fold increase in the number of blood vessels expressing the VEGF receptor, FLK-1 in the vascular endothelium. CONCLUSIONS: Repetitive allergen challenge induces lung vasculogenesis which is associated with upregulation of the levels of VEGF and its receptor FLK-1. These results suggest a potential role for angiogenesis in the process of airway remodeling in allergen induced asthma. Funding: GlaxoSmithKline and Am Lung Assoc Fellow Training Grants
656
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
MONDAY
Angiogenesis in Response to Allergen Challenge in a Murine Model of Asthma S. S. Aceves, S. Y. Lee, J. Y. Cho, D. H. Broide; Division of Allergy, Immunology, University of California, San Diego, La Jolla, CA. RATIONALE: Airways of patients with fatal asthma are edematous and contain increased vasculature. Recent reports have demonstrated that there is increased expression of proangiogenic cytokines in patients with untreated asthma as well as increased expression of anti-angiogenic molecules in patients who have controlled asthma. METHODS: Using a murine model of ova induced asthma in which mice are exposed to repetitive ova challenge for 1–3 months, we have studied the extent of angiogenesis as well as the expression levels of various molecules and growth factors involved in vasculogenesis in response to allergen challenge. RESULTS: Following ova challenge, there is a significant increase in the vascularity in the lungs of ova challenged compared to non-ova challenged mice as assessed by image analysis (0.30 ± 0.07 vs. 0.04 ± 0.02) (p=0.05). The increase in lung vascularity following repetitive ova challenge is associated with increased levels of expression of the angiogenic growth factor VEGF in BAL fluid from ova challenged mice compared to non-ova challenged mice as assessed by ELISA (p=0.05). In addition, we show a 5-fold increase in the number of blood vessels expressing the VEGF receptor, FLK-1 in the vascular endothelium. CONCLUSIONS: Repetitive allergen challenge induces lung vasculogenesis which is associated with upregulation of the levels of VEGF and its receptor FLK-1. These results suggest a potential role for angiogenesis in the process of airway remodeling in allergen induced asthma. Funding: GlaxoSmithKline and Am Lung Assoc Fellow Training Grants
656
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
MONDAY