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Title: Placental Growth Factor Contributes to Bronchial Neutrophilic Inflammation and Edema in Allergic Asthma
Authors: Bobic, Sonja ×
Seys, Sven
De Vooght, Vanessa
Callebaut, Ina
Hox, Valérie
Dooms, Christophe
Vinckier, Stefan
Jonckx, Bart
Saint-Remy, Jean-Marie
Stassen, Jean-Marie
Bullens, Dominique
Ceuppens, Jan
Carmeliet, Peter
Hellings, Peter #
Issue Date: Feb-2012
Publisher: American Lung Association
Series Title: American Journal of Respiratory Cell and Molecular Biology vol:46 issue:6 pages:781-789
Abstract: Rationale. Placental growth factor (PlGF) and its receptor vascular endothelial growth factor receptor 1 (VEGFR1) play an important role in pathological conditions related to angiogenesis, vascular leakage and inflammation. The aim of this study is to investigate their contribution to inflammation and edema formation in allergic asthma. Methods. Expression of PlGF and VEGFR1 was measured in induced sputum of asthma patients (n=11) and healthy subjects (n=11), and bronchial biopsies of HDM-allergic patients stimulated with HDM-allergens. Effects of endonasal administration of hPlGF-2 and PlGF deficiency on inflammation and edema were evaluated in a mouse model of allergic asthma. Migration of human neutrophils in response to hPlGF-2 was tested in vitro. Results. Expression of PlGF and VEGFR1 was significantly higher in sputum of asthma patients, and Der p1 induced PlGF in biopsies from HDM-allergic patients. PlGF was increased in bronchi of OVA-challenged mice compared to controls (65±17 pg/mg vs. 18±1 pg/mg, P<0.01), and VEGFR1 was expressed on bronchial epithelium, endothelium (control mice) and on inflammatory cells (OVA-challenged mice). Endonasal instillation of hPlGF-2 in wt OVA-challenged mice led to an increase in bronchial neutrophils, lung tissue wet/dry ratio and IL-17. PlGF deficient mice showed lower numbers of BAL-infiltrating neutrophils, reduced lung wet/dry ratio and production of IL-17, MIP-2 and GCP-2/LIX compared to wt OVA-challenged mice. hPlGF-2 induced migration of human neutrophils in vitro in a VEGFR1-dependent way. Conclusions. PlGF and its receptor VEGFR1 are up-regulated in allergic asthma and play a pro-inflammatory role by inducing tissue edema, increasing tissue neutrophilia and IL-17 production.
URI: 
ISSN: 1044-1549
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
Occupational, Environmental and Insurance Medicine (-)
Molecular and Vascular Biology
Laboratory of Clinical Immunology
Laboratory of Pediatric Immunology
Pneumology
× corresponding author
# (joint) last author

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