Abstract
A hallmark of chronic infection with lymphatic filarial parasites is the development of lymphatic disease which often results in permanent vasodilation and lymphedema, but all of the mechanisms by which filarial parasites induce pathology are not known. Prior work showed that the asparaginyl-tRNA synthetase (BmAsnRS) of Brugia malayi, an etiological agent of lymphatic filariasis, acts as a physiocrine that binds specifically to interleukin-8 (IL-8) chemokine receptors. Endothelial cells are one of the many cell types that express IL-8 receptors. IL-8 also has been reported previously to induce angiogenesis and vasodilation, however, the effect of BmAsnRS on endothelial cells has not been reported. Therefore, we tested the hypothesis that BmAsnRS might produce physiological changes in endothelial by studying the in vitro effects of BmAsnRS using a human umbilical vein cell line EA.hy926 and six different endothelial cell assays. Our results demonstrated that BmAsnRS produces consistent and statistically significant effects on endothelial cells that are identical to the effects of VEGF, vascular endothelial growth factor. This study supports the idea that new drugs or immunotherapies that counteract the adverse effects of parasite-derived physiocrines may prevent or ameliorate the vascular pathology observed in patients with lymphatic filariasis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aspartate-tRNA Ligase / genetics
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Aspartate-tRNA Ligase / metabolism
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Aspartate-tRNA Ligase / pharmacology*
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Brugia malayi / chemistry*
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Brugia malayi / enzymology
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Cell Line, Transformed
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Cell Proliferation / drug effects*
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Chemotaxis
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Chick Embryo
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Chorioallantoic Membrane / blood supply
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Chorioallantoic Membrane / drug effects
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Helminth Proteins / genetics
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Helminth Proteins / metabolism
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Helminth Proteins / pharmacology*
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Host-Parasite Interactions
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Human Umbilical Vein Endothelial Cells / drug effects
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Human Umbilical Vein Endothelial Cells / metabolism
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Humans
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Neovascularization, Pathologic / chemically induced*
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology
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Protein Binding
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RNA, Transfer, Amino Acyl / genetics
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RNA, Transfer, Amino Acyl / metabolism
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RNA, Transfer, Amino Acyl / pharmacology*
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Receptors, Interleukin-8 / genetics
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Receptors, Interleukin-8 / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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Signal Transduction
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Vascular Endothelial Growth Factor A / pharmacology
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Vasodilation / drug effects*
Substances
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Helminth Proteins
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RNA, Transfer, Amino Acyl
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Receptors, Interleukin-8
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Recombinant Proteins
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Aspartate-tRNA Ligase
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asparaginyl-tRNA synthetase