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(American Journal of Pathology. 2003;163:1321-1327.)
© 2003 American Society for Investigative Pathology

Infectious Angiogenesis

Bartonella bacilliformis Infection Results in Endothelial Production of Angiopoetin-2 and Epidermal Production of Vascular Endothelial Growth Factor

Francesca Cerimele*, Lawrence F. Brown{dagger}, Francisco Bravo{ddagger}, Garret M. Ihler§, Philomene Kouadio§ and Jack L Arbiser*

From the Emory Skin Disease Research Core Center,* Department of Dermatology, Emory University School of Medicine, Boston, Massachusetts; the Department of Pathology,{dagger} Beth Israel Deaconness Hospital, Boston, Massachusetts; the Department of Medical Biochemistry,§ College of Medicine, Texas A&M University System Health Science Center, College Station, Texas; and the Department of Pathology,{ddagger} Universidad Nacionale Cayetano Heredia, Lima, Peru

Pathological angiogenesis, the development of a microvasculature by neoplastic processes, is a critical component of the development of tumors. The role of oncogenes in the induction of angiogenesis has been extensively studied in benign and malignant tumors. However, the role of infection in inducing angiogenesis is not well understood. Verruga peruana is a clinical syndrome caused by the bacterium Bartonella bacilliformis, and is characterized by the development of hemangioma-like lesions, in which bacteria colonize endothelial cells. To gain insight into how this bacteria induces angiogenesis in vivo, we performed in situ hybridization of clinical specimens of verruga peruana for the angiogenesis factors vascular endothelial growth factor (VEGF), its receptors VEGFR1 and VEGFR2, and angiopoietin-2. High-level expression of angiopoietin-2 and VEGF receptors was observed in the endothelium of verruga peruana. Surprisingly, the major source of VEGF production in verruga peruana is the overlying epidermis. Infection of cultured endothelium with B. bacilliformis also resulted in induction of angiopoetin-2 in vitro. These findings imply a collaboration between infected endothelium and overlying epidermis to induce angiogenesis.








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