A hemodynamic response to intravenous adenovirus vector particles is caused by systemic Kupffer cell-mediated activation of endothelial cells

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A hemodynamic response to intravenous adenovirus vector particles is caused by systemic Kupffer cell-mediated activation of endothelial cells. / Schiedner, Gudrun; Bloch, Wilhelm; Hertel, Sabine; Johnston, Marion; Molojavyi, Andrei; Dries, Volker; Varga, Georg; Van Rooijen, Nico; Kochanek, Stefan.

in: Human gene therapy, Jahrgang 14, Nr. 17, 20.11.2003, S. 1631-1641.

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschung

Harvard

Schiedner, G, Bloch, W, Hertel, S, Johnston, M, Molojavyi, A, Dries, V, Varga, G, Van Rooijen, N & Kochanek, S 2003, 'A hemodynamic response to intravenous adenovirus vector particles is caused by systemic Kupffer cell-mediated activation of endothelial cells', Human gene therapy, Jg. 14, Nr. 17, S. 1631-1641. https://doi.org/10.1089/104303403322542275

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Bibtex

@article{fbdfce49d0e3440a912055dd2a047d99,
title = "A hemodynamic response to intravenous adenovirus vector particles is caused by systemic Kupffer cell-mediated activation of endothelial cells",
abstract = "Intravascular injection of adenoviral vectors may result in a toxic and potentially lethal reaction, the mechanism of which is poorly understood. We noted that mice demonstrated a transient change in behavior that was characterized by inactivity and lethargy within minutes after intravenous injection of relatively low doses of adenoviral vectors (including high-capacity gutless vectors). Moreover, immediately after vector injection a significant drop in blood pressure was measured that most probably was caused by the systemic activation of endothelial cells as monitored by detection of phosphorylated Akt/PKB kinase, activated endothelial nitric oxide synthase (eNOS), and nitrotyrosine. The activation of the endothelium was the result of the interaction of viral particles with Kupffer cells, which are resident macrophages of the liver representing the first line of defense of the innate immune system. Surprisingly, the uptake of vector particles by Kupffer cells not only resulted in their strong activation, but also in their nearly complete disappearance from the liver. Our results suggest that the toxicity of intravenously injected adenoviral vectors may be directly linked to the activation and destruction of Kupffer cells.",
keywords = "Adenoviridae, Animals, Blood Pressure, Eicosanoids, Endothelial Cells, Endothelium, Endothelium, Vascular, Enzyme Activation, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Immunohistochemistry, Injections, Intravenous, Kupffer Cells, Liver, Macrophages, Mice, Mice, Inbred C57BL, Microscopy, Electron, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Phosphorylation, Radioimmunoassay, Spleen, Time Factors, Tyrosine",
author = "Gudrun Schiedner and Wilhelm Bloch and Sabine Hertel and Marion Johnston and Andrei Molojavyi and Volker Dries and Georg Varga and {Van Rooijen}, Nico and Stefan Kochanek",
year = "2003",
month = nov,
day = "20",
doi = "10.1089/104303403322542275",
language = "English",
volume = "14",
pages = "1631--1641",
journal = "Human gene therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "17",

}

RIS

TY - JOUR

T1 - A hemodynamic response to intravenous adenovirus vector particles is caused by systemic Kupffer cell-mediated activation of endothelial cells

AU - Schiedner, Gudrun

AU - Bloch, Wilhelm

AU - Hertel, Sabine

AU - Johnston, Marion

AU - Molojavyi, Andrei

AU - Dries, Volker

AU - Varga, Georg

AU - Van Rooijen, Nico

AU - Kochanek, Stefan

PY - 2003/11/20

Y1 - 2003/11/20

N2 - Intravascular injection of adenoviral vectors may result in a toxic and potentially lethal reaction, the mechanism of which is poorly understood. We noted that mice demonstrated a transient change in behavior that was characterized by inactivity and lethargy within minutes after intravenous injection of relatively low doses of adenoviral vectors (including high-capacity gutless vectors). Moreover, immediately after vector injection a significant drop in blood pressure was measured that most probably was caused by the systemic activation of endothelial cells as monitored by detection of phosphorylated Akt/PKB kinase, activated endothelial nitric oxide synthase (eNOS), and nitrotyrosine. The activation of the endothelium was the result of the interaction of viral particles with Kupffer cells, which are resident macrophages of the liver representing the first line of defense of the innate immune system. Surprisingly, the uptake of vector particles by Kupffer cells not only resulted in their strong activation, but also in their nearly complete disappearance from the liver. Our results suggest that the toxicity of intravenously injected adenoviral vectors may be directly linked to the activation and destruction of Kupffer cells.

AB - Intravascular injection of adenoviral vectors may result in a toxic and potentially lethal reaction, the mechanism of which is poorly understood. We noted that mice demonstrated a transient change in behavior that was characterized by inactivity and lethargy within minutes after intravenous injection of relatively low doses of adenoviral vectors (including high-capacity gutless vectors). Moreover, immediately after vector injection a significant drop in blood pressure was measured that most probably was caused by the systemic activation of endothelial cells as monitored by detection of phosphorylated Akt/PKB kinase, activated endothelial nitric oxide synthase (eNOS), and nitrotyrosine. The activation of the endothelium was the result of the interaction of viral particles with Kupffer cells, which are resident macrophages of the liver representing the first line of defense of the innate immune system. Surprisingly, the uptake of vector particles by Kupffer cells not only resulted in their strong activation, but also in their nearly complete disappearance from the liver. Our results suggest that the toxicity of intravenously injected adenoviral vectors may be directly linked to the activation and destruction of Kupffer cells.

KW - Adenoviridae

KW - Animals

KW - Blood Pressure

KW - Eicosanoids

KW - Endothelial Cells

KW - Endothelium

KW - Endothelium, Vascular

KW - Enzyme Activation

KW - Gene Transfer Techniques

KW - Genetic Therapy

KW - Genetic Vectors

KW - Immunohistochemistry

KW - Injections, Intravenous

KW - Kupffer Cells

KW - Liver

KW - Macrophages

KW - Mice

KW - Mice, Inbred C57BL

KW - Microscopy, Electron

KW - Nitric Oxide Synthase

KW - Nitric Oxide Synthase Type II

KW - Nitric Oxide Synthase Type III

KW - Phosphorylation

KW - Radioimmunoassay

KW - Spleen

KW - Time Factors

KW - Tyrosine

U2 - 10.1089/104303403322542275

DO - 10.1089/104303403322542275

M3 - Journal articles

C2 - 14633405

VL - 14

SP - 1631

EP - 1641

JO - Human gene therapy

JF - Human gene therapy

SN - 1043-0342

IS - 17

ER -

ID: 72215