2004
DOI: 10.1182/blood-2003-08-2964
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Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia

Abstract: Vascular endothelial growth factor-A (VEGF-A) expression is up-regulated in several inflammatory diseases including psoriasis, delayed-type hypersensitivity (DTH) reactions, and rheumatoid arthritis. To directly characterize the biologic function of VEGF-A in inflammation, we evaluated experimental DTH reactions induced in the ear skin of transgenic mice that overexpress VEGF-A specifically in the epidermis. VEGF-A transgenic mice underwent a significantly increased inflammatory response that persisted for mor… Show more

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Cited by 283 publications
(369 citation statements)
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“…Not only is it a potent mitogenic factor but it also stimulates ECs to secrete cytokines essential for cell migration and sprouting of new vessels. It has long been supposed that VEGF-A had no association with lymphangiogenesis, however, in two recent experimental studies, VEGF-A overexpression was found to induce formation of new lymph vessels and dilatation of pre-existing ones (Nagy et al, 2002;Kunstfeld et al, 2004). This action was found to be mediated through stimulation of VEGFR-2, a1b1 and a2b1 integrins on the surface of LECs .…”
Section: Discussionmentioning
confidence: 94%
“…Not only is it a potent mitogenic factor but it also stimulates ECs to secrete cytokines essential for cell migration and sprouting of new vessels. It has long been supposed that VEGF-A had no association with lymphangiogenesis, however, in two recent experimental studies, VEGF-A overexpression was found to induce formation of new lymph vessels and dilatation of pre-existing ones (Nagy et al, 2002;Kunstfeld et al, 2004). This action was found to be mediated through stimulation of VEGFR-2, a1b1 and a2b1 integrins on the surface of LECs .…”
Section: Discussionmentioning
confidence: 94%
“…On the other hand, in cases of chronic inflammation, the extensive lymphatic remodeling that occurs can have detrimental affects on normal immune function [1,105,106]. Hyperplastic lymphatics in chronic diseases such as psoriasis, inflammatory bowel disease, chronically-inflamed skin disease and rheumatoid arthritis have negative implications for disease resolution.…”
Section: Chronic Inflammationmentioning
confidence: 99%
“…Hyperplastic lymphatics in chronic diseases such as psoriasis, inflammatory bowel disease, chronically-inflamed skin disease and rheumatoid arthritis have negative implications for disease resolution. For these conditions, treatment with anti-VEGF antibodies can, in some cases, promote disease resolution [106][107][108][109]. Furthermore, while vascular angiogenesis can be reversed in chronic inflammation, lymphangiogenic structures seem to persist [103,110].…”
Section: Chronic Inflammationmentioning
confidence: 99%
“…In addition, other inXammatory diseases seem to be associated with lymphatic activation and dysfunction. For example, lymphatic hyperplasia is observed in UVB-irradiation-induced skin inXammation, in a mouse model of chronic skin inXammation resembling psoriasis, and in human psoriatic skin lesions (Kajiya et al 2006;Kunstfeld et al 2004). In chronic airway inXammation induced by Mycoplasma pulmonis, a massive lymphangiogenesis is induced by VEGF-C/-D-producing inXammatory cells, and its blocking resulted in bronchial lymphedema, thus demonstrating the importance of lymphangiogenesis for compensation of vascular leakage during the inXammation (Baluk et al 2005).…”
Section: Inxammationmentioning
confidence: 97%