# Reactive Oxygen and Nitrogen Species on Monocyte and Macrophage Biology

## TL;DR

This paper reviews how reactive oxygen and nitrogen species influence monocyte and macrophage functions and their roles in inflammation and disease.

## Contribution

The paper synthesizes current evidence on ROS and RNS in monocyte/macrophage biology and highlights emerging therapeutic strategies.

## Key findings

- ROS and RNS regulate monocyte/macrophage survival, migration, and effector functions through redox-sensitive pathways.
- Oxidative stress promotes M1 macrophage polarization and worsens chronic inflammatory diseases like atherosclerosis.
- Therapeutic strategies targeting redox balance show promise for treating cardiovascular and immune-mediated diseases.

## Abstract

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are central regulators of monocyte and macrophage biology, shaping their survival, differentiation, migration, and effector functions. In monocytes and macrophages, ROS and RNS arise from endogenous sources, such as mitochondria, NADPH oxidases, and myeloperoxidase, and from exogenous stimuli including pathogens, damaged tissues, and environmental oxidants. These reactive intermediates converge on redox-sensitive pathways such as NF-κB, Nrf2/HO-1, mitochondrial ROS signalling, and the NLRP3 inflammasome, thereby integrating metabolic stress with inflammatory activation. Redox balance is a key determinant of macrophage polarization: heightened ROS and RNS production drives pro-inflammatory M1 programs, whereas tightly regulated oxidative signalling supports M2 phenotypes associated with tissue repair and resolution. In chronic inflammatory disorders, notably atherosclerosis, oxidative stress amplifies monocyte recruitment, foam-cell formation, plaque instability, and maladaptive immunometabolic responses. The aim of this review is to recapitulate the major sources and functions of ROS and RNS in monocytes and macrophages and to synthesize current evidence on how these pathways collectively maintain or disrupt immune homeostasis. We further highlight emerging therapeutic strategies, such as NOX inhibitors, mitochondrial-targeted antioxidants, and Nrf2 activators, that seek to restore redox balance and offer promising avenues for the treatment of cardiovascular and immune-mediated diseases.