Document Type
Article
Publication Date
2008
College/Unit
School of Medicine
Department/Program/Center
Physiology, Pharmacology & Neuroscience
Abstract
Background
Lyme disease is a common vector-borne disease caused by the spirochete Borrelia burgdorferi(Bb), which manifests as systemic and targeted tissue inflammation. Both in vitro and in vivostudies have shown that Bb-induced inflammation is primarily host-mediated, via cytokine or chemokine production that promotes leukocyte adhesion/migration. Whether Bb produces mediators that can directly alter the vascular permeability in vivo has not been investigated. The objective of the present study was to investigate if Bb produces a mediator(s) that can directly activate endothelial cells resulting in increases in permeability in intact microvessels in the absence of blood cells.
Methodology/Principal Findings
The effects of cell-free, spent culture medium from virulent (B31-A3) and avirulent (B31-A) B. burgdorferi on microvessel permeability and endothelial calcium concentration, [Ca2+]i, were examined in individually perfused rat mesenteric venules. Microvessel permeability was determined by measuring hydraulic conductivity (Lp). Endothelial [Ca2+]i, a necessary signal initiating hyperpermeability, was measured in Fura-2 loaded microvessels. B31-A3 spent medium caused a rapid and transient increase in Lp and endothelial [Ca2+]i. Within 2–5 min, the mean peak Lp increased to 5.6±0.9 times the control, and endothelial [Ca2+]i increased from 113±11 nM to a mean peak value of 324±35 nM. In contrast, neither endothelial [Ca2+]i nor Lp was altered by B31-A spent medium.
Conclusions/Significance
A mediator(s) produced by virulent Bb under culture conditions directly activates endothelial cells, resulting in increases in microvessel permeability. Most importantly, the production of this mediator is associated with Bb virulence and is likely produced by one or more of the 8 plasmid(s) missing from strain B31-A.
Digital Commons Citation
Zhou, Xueping; Miller, Michael R.; Motaleb, Md; Charon, Nyles W.; and He, Pingnian, "Spent Culture Medium from Virulent Borrelia burgdorferi Increases Permeability of Individually Perfused Microvessels of Rat Mesentery" (2008). Faculty & Staff Scholarship. 2856.
https://researchrepository.wvu.edu/faculty_publications/2856
Source Citation
Zhou X, Miller MR, Motaleb M, Charon NW, He P (2008) Spent Culture Medium from Virulent Borrelia burgdorferi Increases Permeability of Individually Perfused Microvessels of Rat Mesentery. PLoS ONE 3(12): e4101. https://doi.org/10.1371/journal.pone.0004101
Comments
© 2008 Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.