Evidence of a leading role for VEGF in Bartonella henselae-induced endothelial cell proliferations

Bartonella henselae causes the vasculoproliferative disorders bacillary ang iomatosis (BA) and bacillary peliosis (BP). The pathomechanisms of these tu morous proliferations are unknown. Our results suggest a novel bacterial tw o-step pathogenicity strategy, in which the pathogen triggers growth factor production for subsequent proliferation of its own host cells. In fact, B. henselae induces host cell production of the angiogenic factor vascular en dothelial growth factor (VEGF), leading to proliferation of endothelial cel ls. The presence of B. henselae pili was associated with host cell VEGF pro duction, as a Pil(-) mutant of B. henselae was unable to induce VEGF produc tion. In turn, VEGF-stimulated, endothelial cells promoted the growth of B. henselae. Immunohistochemistry for VEGF in specimens from patients with BA or BP revealed increased VEGF expression in vivo. These findings suggest a novel bacteria-dependent mechanism of tumour growth.