Functions of ROS in Macrophages and Antimicrobial Immunity

Abstract

Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS for macrophage-mediated immunity is unquestioned. Their functions comprise direct antimicrobial activity against bacteria and parasites as well as redox-regulation of immune signaling and induction of inflammasome activation. However, only a few studies have performed in-depth ROS analyses and even fewer have identified the precise redox-regulated target molecules. In this review, we will give a brief introduction to ROS and their sources in macrophages, summarize the versatile roles of ROS in direct and indirect antimicrobial immune defense, and provide an overview of commonly used ROS probes, scavengers and inhibitors.

Reactive Oxygen Species: Not Omnipresent but Important in Many Locations

“…In recent years, more and more studies supported the model-and highlighted the importance-of localized cellular ROS production in direct vicinity of the redox target (Meinhard and Grill, 2001;Veal et al, 2007;Go and Jones, 2008;Craig and Slauch, 2009;West et al, 2011a;Wink et al, 2011;Zhou et al, 2011;Al-Mehdi et al, 2012;Naviaux, 2012;Allan et al, 2014;Romero et al, 2014;Geng et al, 2015;Gluschko et al, 2018;Herb et al, 2019b;Acin-Perez et al, 2020;Beretta et al, 2020;Chanin et al, 2020;Miller et al, 2020;Sies and Jones, 2020;Herb and Schramm, 2021;Ligeon et al, 2021b;Sies, 2021;Wong et al, 2021). Therefore, the model of ROS molecules as "omnipresent and freely diffusing throughout the cell" should always be interpreted carefully in the context of research and highly depends on the proper use of ROS probes, scavengers and inhibitors.…”

“…, xanthine oxidase (Nomura et al, 2014;Al-Shehri et al, 2020), peroxisomes (Lismont et al, 2015;Fransen et al, 2017;Shai et al, 2018) and cytochrome P450 oxidases (Omura and Sato, 1962;Zhang et al, 2020) can be responsible for cellular ROS production and it highly depends on the stimulus and the cell type whether a single or multiple ROS sources are activated, for how long this occurs and for what purpose (Banfi et al, 2004;Gavazzi et al, 2006;Bedard and Krause, 2007;Aguirre and Lambeth, 2010;Brand, 2010;Dikalova et al, 2010;Donko et al, 2010;Carnesecchi et al, 2011;Al-Mehdi et al, 2012;Lanciano et al, 2013;Kim et al, 2014;Lambeth and Neish, 2014;Ives et al, 2015;Xu et al, 2017;Herb et al, 2019b;Hernansanz-Agustin et al, 2020;Herb and Schramm, 2021).…”

“…The most commonly used ROS probe for detection of mitochondrial ROS is MitoSOX, which measures O 2 − exclusively inside the mitochondrial matrix (Robinson et al, 2006;Mukhopadhyay et al, 2007;Ernst et al, 2021). However, since the ETC complexes show compartment-specific differences concerning ROS production (Fridovich, 1997;Murphy, 2009;Brand, 2010;West et al, 2011b;Herb and Schramm, 2021), this probe can only be used to measure ROS production inside mitochondria and, therefore, other cellular compartments should always be analyzed in addition. In healthy, undamaged mitochondria, ROS cannot escape the mitochondrial matrix because of the very effective antioxidative defense system (Roca and Ramakrishnan, 2013;Briston et al, 2017;Hos et al, 2017;Hernansanz-Agustin et al, 2020;Lin et al, 2020;Wang et al, 2020;Zhao et al, 2020).…”

Silver(I) and Copper(II) Complexes of 1,10-Phenanthroline-5,6-Dione Against Phialophora verrucosa: A Focus on the Interaction With Human Macrophages and Galleria mellonella Larvae

“…From the current study, it is evident that addition of the test compounds improved the antifungal action of macrophages. The increase of compoundtreated P. verrucosa susceptibility to macrophage killing could be related to an increase in the production of reactive oxygen species by these phagocytes since the respiratory burst is one of the most important mechanisms for the antimicrobial immunity of phagocytic cells (Herb and Schramm, 2021). Thus, the enhanced ability of macrophages to combat the fungal infection could be explained by the direct action of the test compounds on the intracellular conidia, and by the induction of intracellular macrophage mechanisms that mediate the antimicrobial immune responses, just as has previously been reported in regard to the anti-mycobacterial and antitumoral activities of phen-and phendione-based complexes (Kellett et al, 2011;McCarron et al, 2018).…”

Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling

“…It is known that hypoxic conditions affect oxidative stress. There are several sources of ROS, including the respiratory electron transport chain in mitochondria, the family of NADPH-oxidase enzymes, xanthine oxidase, peroxisomes, cytochrome p450 enzymes, cyclooxygenase, and lipoxygenase [81]. Mitochondria are influenced by HIF-1α during the cellular respiration process.…”