Macrophage Extracellular Traps in Health and Disease: Current Concepts, Pathogenic Mechanisms and Clinical Implications

Macrophage extracellular traps (METs) are chromatin-based structures released by activated macrophages and are increasingly recognized as distinct, context-dependent effectors of innate immunity. Although initially described in antimicrobial defense, METs are now implicated in sterile inflammation, autoimmunity, fibrosis, metabolic and vascular injury, organ-specific damage, and cancer. This review integrates dispersed evidence on MET biology across physiological and pathological settings, moving beyond neutrophil-centered interpretations of extracellular trap biology. We summarize the molecular composition, structural heterogeneity, major forms of METosis, and key regulatory pathways, including PAD-dependent chromatin remodeling, reactive oxygen species and calcium signaling, mitochondrial DNA release, extracellular DNA sensing, protease-mediated injury, and macrophage–stromal crosstalk. We also discuss the dual nature of METs as protective structures that can contain pathogens and amplify early innate responses, but also as pathogenic platforms when excessive, persistent, or insufficiently cleared. Overall, current evidence supports METs as functionally versatile macrophage-derived immune structures whose biological effects depend on the stimulus, tissue microenvironment, and disease context. By providing a unified framework, this review highlights the relevance of METs as potential biomarkers and therapeutic targets in inflammatory, fibrotic, vascular, autoimmune, and malignant diseases.