FIGURE 2.

Activation of the phagocytic NADPH oxidase (Nox2, gp91phox) by noise (Kroller-Schon et al., 2018) and role of LysM-positive myelomonocytic cells for noise-induced cardiovascular inflammation and damage (Frenis et al., 2021). Noise causes cerebral and vascular ROS formation as envisaged by more pronounced dihydroethidium (DHE)-derived red fluorescence in cerebral and aortic cryo-sections that was partially corrected in gp91phox (Nox2) knockout mice (representative stainings). Nox2 activation by noise was probably based on angiotensin-II (ATII)-dependent AT1-receptor activation with subsequent activation of phospholipase C and diacylglycerol (DAG) formation, a strong protein kinase C (PKC) activator. PKC activation was documented by noise-triggered phosphorylation of the PKC target myristoylated, alanine-rich C kinase substrate (MARCKS) as well as phosphorylation of p47phox at serine 328, a regulatory cytosolic subunit of Nox2. Translocation of pSer328-p47phox, among other cytosolic regulators, to the cytoplasmatic membrane-bound gp91phox leads to full activation of Nox2 and subsequent superoxide formation. Genetic ablation by treatment of mice with LysM-positive cell (myelomonocytic) specific overexpression of an inducible diphtheria toxin receptor (LysM^iDTR) with low dose diphtheria toxin (Wenzel et al., 2011). Mice free of LysM-positive cells showed no noise-dependent infiltration of monocytes, macrophages or granulocytes and preserved endothelial function, normal blood pressure and no aortic oxidative stress indicating that LysM-positive cell ablation protects the periphery from noise-induced damage. In contrast, microglia in the brain of LysM^iDTR mice were not ablated by diphtheria toxin and noise-induced neuroinflammation, cerebral oxidative stress and release of stress hormones was not prevented. Image was created using Biorender.com. DHE staining images were reused from (Kroller-Schon et al., 2018) with permission.