Angiotensin-converting enzyme enhances the oxidative response and bactericidal activity of neutrophils.

Blood
Zakir KhanKenneth E Bernstein

Abstract

Angiotensin-converting enzyme (ACE) inhibitors are widely used to reduce blood pressure. Here, we examined if an ACE is important for the antibacterial effectiveness of neutrophils. ACE knockout mice or mice treated with an ACE inhibitor were more susceptible to bacterial infection by methicillin-resistant Staphylococcus aureus (MRSA). In contrast, mice overexpressing ACE in neutrophils (NeuACE mice) have increased resistance to MRSA and better in vitro killing of MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae ACE overexpression increased neutrophil production of reactive oxygen species (ROS) following MRSA challenge, an effect independent of the angiotensin II AT1 receptor. Specifically, as compared with wild-type (WT) mice, there was a marked increase of superoxide generation (>twofold, P < .0005) in NeuACE neutrophils following infection, whereas ACE knockout neutrophils decreased superoxide production. Analysis of membrane p47-phox and p67-phox indicates that ACE increases reduced NAD phosphate oxidase activity but does not increase expression of these subunits. Increased ROS generation mediates the enhanced bacterial resistance of NeuACE mice because the enhanced resistance is lost with DPI (an inhibitor of ROS pr...Continue Reading

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Citations

Jan 31, 2018·Nature Reviews. Nephrology·R Ariel Gomez, Maria Luisa S Sequeira-Lopez
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Jun 9, 2020·Cellular & Molecular Biology Letters·Duo-Yao CaoZakir Khan
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Oct 17, 2019·Biochemical and Biophysical Research Communications·Derick Okwan-DuoduKenneth E Bernstein
Apr 2, 2021·Scientific Reports·Brian C BelyeaR Ariel Gomez
Mar 31, 2021·Molecular and Cellular Endocrinology·Jorge F GianiKenneth E Bernstein
Apr 1, 2021·Molecular and Cellular Endocrinology·Jacqueline M EmathingerSusan B Gurley
May 25, 2021·Journal of Immunological Methods·Ling LiuYi Yang
Aug 21, 2021·International Journal of General Medicine·Daguan ZhangXuecheng Sun
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Sep 26, 2021·Leukemia·Lucie de BeauchampG Vignir Helgason
Nov 4, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Vatsala Khurana, Binita Goswami

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