Novel and converging ways of NOX2 and SOD3 in trafficking and redox signaling in macrophages
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
Standard
Novel and converging ways of NOX2 and SOD3 in trafficking and redox signaling in macrophages. / Petersen, Steen Vang; Poulsen, Nanna Bach; Matthiesen, Cecilie Linneberg; Vilhardt, Frederik.
I: Antioxidants, Bind 10, Nr. 2, 172, 2021, s. 1-16.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Novel and converging ways of NOX2 and SOD3 in trafficking and redox signaling in macrophages
AU - Petersen, Steen Vang
AU - Poulsen, Nanna Bach
AU - Matthiesen, Cecilie Linneberg
AU - Vilhardt, Frederik
PY - 2021
Y1 - 2021
N2 - Macrophages and related tissue macrophage populations use the classical NADPH oxidase (NOX2) for the regulated production of superoxide and derived oxidants for pathogen combat and redox signaling. With an emphasis on macrophages, we discuss how sorting into secretory storage vesicles, agonist-responsive membrane trafficking, and segregation into sphingolipid and cholesterol-enriched microdomains (lipid rafts) determine the subcellular distribution and spatial organization of NOX2 and superoxide dismutase-3 (SOD3). We discuss how inflammatory activation of macrophages, in part through small GTPase Rab27A/B regulation of the secretory compartments, mediates the coalescence of these two proteins on the cell surface to deliver a focalized hydrogen peroxide output. In interplay with membrane-embedded oxidant transporters and redox sensitive target proteins, this arrangement allows for the autocrine and paracrine signaling, which govern macrophage activation states and transcriptional programs. By discussing examples of autocrine and paracrine redox signaling, we highlight why formation of spatiotemporal microenvironments where produced superoxide is rapidly converted to hydrogen peroxide and conveyed immediately to reach redox targets in proximal vicinity is required for efficient redox signaling. Finally, we discuss the recent discovery of macrophage-derived exosomes as vehicles of NOX2 holoenzyme export to other cells.
AB - Macrophages and related tissue macrophage populations use the classical NADPH oxidase (NOX2) for the regulated production of superoxide and derived oxidants for pathogen combat and redox signaling. With an emphasis on macrophages, we discuss how sorting into secretory storage vesicles, agonist-responsive membrane trafficking, and segregation into sphingolipid and cholesterol-enriched microdomains (lipid rafts) determine the subcellular distribution and spatial organization of NOX2 and superoxide dismutase-3 (SOD3). We discuss how inflammatory activation of macrophages, in part through small GTPase Rab27A/B regulation of the secretory compartments, mediates the coalescence of these two proteins on the cell surface to deliver a focalized hydrogen peroxide output. In interplay with membrane-embedded oxidant transporters and redox sensitive target proteins, this arrangement allows for the autocrine and paracrine signaling, which govern macrophage activation states and transcriptional programs. By discussing examples of autocrine and paracrine redox signaling, we highlight why formation of spatiotemporal microenvironments where produced superoxide is rapidly converted to hydrogen peroxide and conveyed immediately to reach redox targets in proximal vicinity is required for efficient redox signaling. Finally, we discuss the recent discovery of macrophage-derived exosomes as vehicles of NOX2 holoenzyme export to other cells.
KW - Cellular sorting
KW - Hydrogen peroxide
KW - Macrophages
KW - Membrane trafficking
KW - NOX2
KW - Rab27
KW - Redox signaling
KW - SOD3
KW - Superoxide
U2 - 10.3390/antiox10020172
DO - 10.3390/antiox10020172
M3 - Review
C2 - 33503855
AN - SCOPUS:85099932017
VL - 10
SP - 1
EP - 16
JO - Antioxidants
JF - Antioxidants
SN - 2076-3921
IS - 2
M1 - 172
ER -
ID: 256512831