Manipulation of vascular function by blood flukes?

Abstract

Schistosomes (blood flukes) are long lived, intravascular parasites that afflict ~200 million people worldwide. Here we review the potential ability of these parasites to exert control on local vascular physiology. We examine schistosome kallikrein-like proteins that drive vasodilation. We review biogenic amine metabolism in the parasites that involve the vasodilator histamine and its receptors and the vasoconstrictor serotonin and its receptor. Schistosomes can trigger the release of histamine from host cells and can import serotonin. We consider the ability of schistosomes to generate and release the eicosanoid vasodilators PGD(2) and PGE(2) and the vasoconstrictors LTB(4) and LTC(4). The literature on nitric oxide metabolism in these blood flukes is assessed. Finally the potential impact of other schistosome metabolic processes (e.g. exogenous adenosine generation and acetylcholine degradation) on vascular function is appraised. An increased understanding of these processes could lead to novel anti-parasitics as well as new therapies to treat vascular dysfunction.

Fig. 1

Haemotoxylin and eosin stained section of the vasculature of a mouse infected 6 weeks previously with Schistosoma mansoni. A cross section of an adult male and female worm is shown. The female is contained within the male’s gynaecophoric canal. The vascular endothelium bounding the couple is indicated (arrowheads). Aspects of schistosome biochemistry that may pertain to vascular physiology are highlighted in 4 boxes. Box 1 (top) lists metabolites that could impinge powerfully on host vasculature. These include the schistosome kallikrein-like protease (SK1 and/or SmSP1), histamine and NO. The second group of metabolites, listed in box 2, include molecules that the worms are known to produce and release, at lease in vitro. These include the eicosanoids PGD₂ and PGE₂, lactate and potassium ions. Box 3 highlights the fact that some tegumental ecto-enzymes (e.g. alkaline phosphatase and acetylcholinesterase) may to exert an effect on vascular function. Box 4 (bottom) highlights the ability of the parasites to take up the vasoconstrictor serotonin. The while arrows indicate the potential movement of the selected metabolites into, or out of, the parasites.