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. This study investigated their contributions to
inflammation and the formation of
edema in allergic
asthma. The expression of PlGF and VEGFR1 was measured in induced sputum of patients with
asthma (n = 11) and healthy subjects (n = 11), and in bronchial biopsies of house dust mite (HDM)-allergic patients stimulated with HDM
allergens. The effects of the endonasal administration of human PlGF-2 and PlGF deficiency on
inflammation and
edema were evaluated in a murine model of allergic
asthma. The migration of human neutrophils in response to hPlGF-2 was tested in vitro. The expression of PlGF and VEGFR1 was significantly higher in the sputum of patients with
asthma, and in Der p 1-induced PlGF in biopsies from HDM-allergic patients. PlGF was increased in the bronchi of
ovalbumin (OVA)-challenged mice compared with control mice (65 ± 17 pg/mg versus 18 ± 1 pg/mg, respectively; P < 0.01), and VEGFR1 was expressed in bronchial epithelium, endothelium (control mice), and inflammatory cells (OVA-challenged mice). The endonasal instillation of hPlGF-2 in wild-type, 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, a reduced
lung wet/dry ratio, and lower production of
IL-17, macrophage inflammatory protein-2, and
granulocyte chemotactic protein-2/LPS-induced
chemokine compared with wild-type, OVA-challenged mice. hPlGF-2 induced the migration of human neutrophils in vitro in a VEGFR1-dependent way. PlGF and its receptor VEGFR1 are up-regulated in allergic
asthma and play a proinflammatory role by inducing tissue
edema, and increasing tissue neutrophilia and the production of
IL-17.