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Brugia malayi Asparaginyl-tRNA Synthetase Stimulates Endothelial Cell Proliferation, Vasodilation and Angiogenesis. PLoS One 2016;11(1):e0146132

Date

01/12/2016

Pubmed ID

26751209

Pubmed Central ID

PMC4709172

DOI

10.1371/journal.pone.0146132

Scopus ID

2-s2.0-84954562439 (requires institutional sign-in at Scopus site)   11 Citations

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.

Author List

D JJ, Dhanraj M, Solaiappan S, Sivanesan S, Kron M, Dhanasekaran A

Author

Michael Kron MD Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Aspartate-tRNA Ligase
Brugia malayi
Cell Line, Transformed
Cell Proliferation
Chemotaxis
Chick Embryo
Chorioallantoic Membrane
Escherichia coli
Gene Expression
Helminth Proteins
Host-Parasite Interactions
Human Umbilical Vein Endothelial Cells
Humans
Neovascularization, Pathologic
Protein Binding
RNA, Transfer, Amino Acyl
Receptors, Interleukin-8
Recombinant Proteins
Signal Transduction
Vascular Endothelial Growth Factor A
Vasodilation