Spent culture medium from virulent Borrelia burgdorferi increases permeability of individually perfused microvessels of rat mesentery

Xueping Zhou, Michael R. Miller, Md Motaleb, Nyles W. Charon, Ping He

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 vivo studies 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.

Original languageEnglish (US)
Article numbere4101
JournalPloS one
Volume3
Issue number12
DOIs
StatePublished - Dec 31 2008

Fingerprint

mesentery
Borrelia burgdorferi
Mesentery
Endothelial cells
Microvessels
Culture Media
Rats
Permeability
permeability
culture media
Fura-2
calcium
rats
Hydraulic conductivity
Chemokines
Cell culture
Plasmids
Blood
Adhesion
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

@article{761c365921c84122b6f0be4bda526f4e,
title = "Spent culture medium from virulent Borrelia burgdorferi increases permeability of individually perfused microvessels of rat mesentery",
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 vivo studies 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.",
author = "Xueping Zhou and Miller, {Michael R.} and Md Motaleb and Charon, {Nyles W.} and Ping He",
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language = "English (US)",
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Spent culture medium from virulent Borrelia burgdorferi increases permeability of individually perfused microvessels of rat mesentery. / Zhou, Xueping; Miller, Michael R.; Motaleb, Md; Charon, Nyles W.; He, Ping.

In: PloS one, Vol. 3, No. 12, e4101, 31.12.2008.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Spent culture medium from virulent Borrelia burgdorferi increases permeability of individually perfused microvessels of rat mesentery

AU - Zhou, Xueping

AU - Miller, Michael R.

AU - Motaleb, Md

AU - Charon, Nyles W.

AU - He, Ping

PY - 2008/12/31

Y1 - 2008/12/31

N2 - 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 vivo studies 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.

AB - 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 vivo studies 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.

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