Morphological Signatures of Neutrophil Extracellular Traps: From Ultra-Structural Organization to Tissue Remodeling and Pathophysiological Contexts

Neutrophil extracellular traps (NETs) are web-like networks of decondensed chromatin fibers decorated with histones and neutrophil granular proteins that neutrophils release as part of the innate immune response.These structures, first observed by high-resolution electron microscopy as smooth DNA fibers, are pivotal in immobilizing pathogens.However, excessive NET formation is a double-edged sword.On one hand, NETs contribute to host defense; on the other, their accumulation can cause vessel occlusion, cytotoxicity to host cells, and persistent inflammation.This scientific review provides a comprehensive histological and pathological perspective on NETs, from their ultrastructural organization to their roles in tissue remodeling across various organ systems.We place a particular emphasis on reproductive tissues, where NETs have been implicated in conditions from infertility to pregnancy complications.Additionally, we explore NET-associated pathology in pulmonary diseases (e.g.acute respiratory distress syndrome and chronic airway diseases), vascular systems (atherothrombosis and immunothrombosis), and other contexts such as autoimmune disorders and cancer.We discuss how NETs are identified in tissue (e.g. by extracellular DNA co-localized with neutrophil enzymes), the morphological signatures they present (e.g.fibrillar chromatin networks or aggregated DNA-protein complexes), and how these structures drive tissue damage or remodeling.In conclusion, while NETs are essential for trapping microbes, their dysregulation leads to collateral damage in tissues.Understanding NET morphology in situ and its consequences provides insight into disease mechanisms and highlights potential therapeutic strategies to mitigate tissue injury while preserving host defense.