Characterisation and partial purification of Schistosoma mansoni egg-derived pro-angiogenic factor

Abstract

Pathogenesis of Schistosoma mansoni infection is due to the accumulation of eggs in the liver and intestine of the host followed by granuloma formation and fibrosis at the site of egg embolism. Nevertheless, total hepatic blood flow and hepatic function appear to be maintained by neovascularisation of the periportal fibrotic tissue. Here we demonstrate that intact live eggs, excretory/secretory products of eggs and the extracts of homogenised eggs stimulate the proliferation and migration of endothelial cells. Formation of endothelial capillary-like outgrowths, as well as, the activation of p42/p44 mitogen-activated protein kinase signal transduction pathway was stimulated by egg extracts, whereas other stages of the schistosome life-cycle did not exhibit such activity. We have characterised and partially purified the pro-angiogenic factor. The active pro-angiogenic component was fast-acting, heat-stable, protease-resistant, weakly heparin-binding and a non-lipid. It could be extracted with acidified ethanol or a hot acetic acid solution and could be partially purified by reverse-phase HPLC. The S. mansoni egg-derived pro-angiogenic factor, described here, may directly contribute to vascular remodelling in the liver and illustrates how helminth parasites may modulate angiogenesis.