title: Leishmania major Infection-Induced VEGF-A/VEGFR-2 Signaling Promotes Lymphangiogenesis That Controls Disease.
abstract: Cutaneous leishmaniasis causes a spectrum of diseases from self-healing to severe nonhealing lesions. Defining the factors contributing to lesion resolution may help in developing new therapies for those patients with chronic disease. We found that infection with Leishmania major increases the expression of vascular endothelial growth factor-A and vascular endothelial growth factor receptor (VEGFR)-2 and is associated with significant changes in the blood and lymphatic vasculature at the site of infection. Ab blockade of VEGFR-2 during infection led to a reduction in lymphatic endothelial cell proliferation and simultaneously increased lesion size without altering the parasite burden. These data show that L. major infection initiates enhanced vascular endothelial growth factor-A/VEGFR-2 signaling and suggest that VEGFR-2-dependent lymphangiogenesis is a mechanism that restricts tissue inflammation in leishmaniasis.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; and.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Weinkopff
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Konradt
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; and.
authors.forename: David A
authors.initials: DA
authors.lastname: Christian
authors.affiliation: Biophysical Eng'g Labs, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Discher
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; and.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; and pscott@vet.upenn.edu.
authors.forename: Phillip
authors.initials: P
authors.lastname: Scott
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D020405:Dermis / Q000469:parasitology / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2