title: Lymphangiogenesis in rat asthma model.
abstract: Although bronchial angiogenesis has been well documented in allergic asthma, lymphangiogenesis has not been widely studied. Therefore, we evaluated changes in lung lymphatics in a rat model of allergen-induced asthma using house dust mite (Der p 1; 100 μg/challenge). Additionally, properties of isolated lung lymphatic endothelial cells (CD45-, CD141+, LYVE-1+, Prox-1+) were studied in vitro. Three weeks after the onset of intranasal allergen exposure (twice-weekly), an increase in the number of lung lymphatic vessels was measured (34% increase) by lung morphometry. New lymphatic structures were seen predominantly in the peribronchial and periarterial interstitial space but also surrounding large airways. Isolated lymphatic endothelial cells from sensitized lungs showed enhanced proliferation (% Ki67+), chemotaxis, and tube formation (number and length) compared to lymphatic endothelial cells isolated from naive rat lungs. This hyper-proliferative lymphangiogenic phenotype was preserved through multiple cell passages (2-8). Lymphatic endothelial cells isolated from naive and HDM-sensitized rats produced similar in vitro levels of VEGF-C, VEGF-D, and VEGFR3 protein, each recognized as critical lymphangiogenic factors. Inhibition with anti-VEGFR (axitinib, 0.1 μM) blocked proliferation and chemotaxis. Results suggest that in vivo sensitization causes fundamental changes to lymphatic endothelium, which are retained in vitro, and may relate to VEGFR downstream signaling.
authors: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD, 21224, USA.
authors: Aigul
authors: A
authors: Moldobaeva
authors: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD, 21224, USA.
authors: John
authors: J
authors: Jenkins
authors: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD, 21224, USA.
authors: Qiong
authors: Q
authors: Zhong
authors: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD, 21224, USA. wagnerem@jhmi.edu.
authors: Elizabeth M
authors: EM
authors: Wagner
mesh_terms: D000818:Animals; D001249:Asthma / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005629:Frozen Sections; D008168:Lung / Q000473:pathology; D042583:Lymphangiogenesis; D008297:Male; D039981:Pyroglyphidae / Q000502:physiology; D011914:Rats, Inbred BN; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism
chemical_list: D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D
keywords: Allergen; Angiogenesis; House dust mite; Lung; Lymphatic vessels