Brugia malayi Asparaginyl-tRNA Synthetase Stimulates Endothelial Cell Proliferation, Vasodilation and Angiogenesis.

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.

• Authors: Jeeva Jothi D, Muthu Dhanraj, Shanmugam Solaiappan, Sanjana Sivanesan, Michael Kron, Anuradha Dhanasekaran
• Journal: PloS one (PLoS One) Vol. 11 Issue 1 Pg. e0146132 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 26751209 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Helminth Proteins
• RNA, Transfer, Amino Acyl
• Receptors, Interleukin-8
• Recombinant Proteins
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Aspartate-tRNA Ligase
• asparaginyl-tRNA synthetase

Topics

• Animals
• Aspartate-tRNA Ligase (genetics, metabolism, pharmacology)
• Brugia malayi (chemistry, enzymology)
• Cell Line, Transformed
• Cell Proliferation (drug effects)
• Chemotaxis
• Chick Embryo
• Chorioallantoic Membrane (blood supply, drug effects)
• Escherichia coli (genetics, metabolism)
• Gene Expression
• Helminth Proteins (genetics, metabolism, pharmacology)
• Host-Parasite Interactions
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Neovascularization, Pathologic (chemically induced, metabolism, pathology)
• Protein Binding
• RNA, Transfer, Amino Acyl (genetics, metabolism, pharmacology)
• Receptors, Interleukin-8 (genetics, metabolism)
• Recombinant Proteins (genetics, metabolism, pharmacology)
• Signal Transduction
• Vascular Endothelial Growth Factor A (pharmacology)
• Vasodilation (drug effects)