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Placental Growth Factor Contributes to Bronchial Neutrophilic Inflammation and Edema in Allergic Asthma.

Authors: Bobic, S  Seys, S  De Vooght, V  Callebaut, I  Hox, V  Dooms, C  Vinckier, S  Jonckx, B  Saint-Remy, JM  Stassen, JM  Bullens, DM  Ceuppens, JL  Carmeliet, P  Hellings, PW 
Citation: Bobic S, etal., Am J Respir Cell Mol Biol. 2012 Feb 3.
Pubmed: (View Article at PubMed) PMID:22268141
DOI: Full-text: DOI:10.1165/rcmb.2011-0152OC

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.

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CRRD Object Information
CRRD ID: 6483605
Created: 2012-05-29
Species: All species
Last Modified: 2012-05-29
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.