Normal IgG downregulates the intracellular superoxide level and attenuates migration and permeability in human aortic endothelial cells isolated from a hypertensive patient

Xiuqing Wang, Qianyu Wang, Zhongjie Sun

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Abstract

The normal IgG, a circulating antibody, is maintained at a constant level in humans. However, little is known regarding whether normal IgG has effects on the function of vascular endothelial cells. The purpose of this study was to investigate whether IgG affects superoxide (O2 .-) generation and cell permeability in human aortic endothelial cells (HAECs) isolated from a hypertensive patient. The effect of normal human IgG on endothelial cell function was investigated in cultured HAECs isolated from a hypertensive patient who died of stroke. The results demonstrated, for the first time, that normal IgG attenuated the intracellular O2 .- level and decreased cell migration, cell permeability, and stress fiber formation in HAECs. IgG significantly decreased Rac1 activity and NADPH oxidase activity but upregulated Mn superoxide dismutase expression in HAECs, which may contribute to the IgG-induced decrease in O2 .- level. It is noted that AMP-activated protein kinase (AMPK) was activated by IgG, as evidenced by increased phosphorylation of AMPK. Interestingly, inhibition of AMPK by an AMPK inhibitor abolished IgG-induced decreases in Rac1 and NADPH oxidase activities and IgG-induced increases in Mn superoxide dismutase expression, suggesting that AMPK is an important mediator of the IgG-induced regulation of these enzymes. Importantly, inhibition of AMPK activity also prevented the IgG-induced decrease in O2 .- levels, cell migration, cell permeability, and stress fiber formation. Therefore, normal human IgG may protect HAECs via activation of AMPK and subsequent decreases in intracellular O2 .-. These findings reveal a previously unidentified role of normal IgG in regulating AMPK and endothelial cell function.

Original languageEnglish (US)
Pages (from-to)818-826
Number of pages9
JournalHypertension
Volume60
Issue number3
DOIs
StatePublished - Sep 1 2012

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Superoxides
Permeability
Down-Regulation
Endothelial Cells
Immunoglobulin G
AMP-Activated Protein Kinases
Stress Fibers
NADPH Oxidase
Superoxide Dismutase
Cell Movement
Protein Kinase Inhibitors
Stroke
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

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title = "Normal IgG downregulates the intracellular superoxide level and attenuates migration and permeability in human aortic endothelial cells isolated from a hypertensive patient",
abstract = "The normal IgG, a circulating antibody, is maintained at a constant level in humans. However, little is known regarding whether normal IgG has effects on the function of vascular endothelial cells. The purpose of this study was to investigate whether IgG affects superoxide (O2 .-) generation and cell permeability in human aortic endothelial cells (HAECs) isolated from a hypertensive patient. The effect of normal human IgG on endothelial cell function was investigated in cultured HAECs isolated from a hypertensive patient who died of stroke. The results demonstrated, for the first time, that normal IgG attenuated the intracellular O2 .- level and decreased cell migration, cell permeability, and stress fiber formation in HAECs. IgG significantly decreased Rac1 activity and NADPH oxidase activity but upregulated Mn superoxide dismutase expression in HAECs, which may contribute to the IgG-induced decrease in O2 .- level. It is noted that AMP-activated protein kinase (AMPK) was activated by IgG, as evidenced by increased phosphorylation of AMPK. Interestingly, inhibition of AMPK by an AMPK inhibitor abolished IgG-induced decreases in Rac1 and NADPH oxidase activities and IgG-induced increases in Mn superoxide dismutase expression, suggesting that AMPK is an important mediator of the IgG-induced regulation of these enzymes. Importantly, inhibition of AMPK activity also prevented the IgG-induced decrease in O2 .- levels, cell migration, cell permeability, and stress fiber formation. Therefore, normal human IgG may protect HAECs via activation of AMPK and subsequent decreases in intracellular O2 .-. These findings reveal a previously unidentified role of normal IgG in regulating AMPK and endothelial cell function.",
author = "Xiuqing Wang and Qianyu Wang and Zhongjie Sun",
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AU - Wang, Qianyu

AU - Sun, Zhongjie

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