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.