<p>Mice were intravenously injected with increasing concentrations of histamine (0.1, 0.5, 2.5, 12.55, 62.5 and 312.5 µg/g) or saline as negative control together with 100 nm green fluorescent microspheres. Tissue samples were whole-mount stained for CD31 (<b>A</b>) and microspheres area density was quantified as indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070459#s2" target="_blank">Materials and Methods</a> (<b>B, C</b>). To establish the dose response of histamine-induced vascular leakage, fluorescent microspheres were injected together with histamine and mice were sacrificed after 1 min (<b>B</b>). To establish the time course of histamine-induced vascular leakage, microspheres were injected after the indicated times of exposure to submaximal concentrations of histamine (62.5 µg/g) and mice were sacrificed within 1 min (<b>C</b>). Values are expressed as mean ± SD (n = 5, saline n = 3). **P<0.01 compared to saline. Scale bar 100 µm.</p