R Adhi Shree, Nambi Nandhana, Radhakrishnan Leela, Prasad Murali Krishna, Ramkumar Kunka Mohanram
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
Curr Vasc Pharmacol. 2024 Oct 30. doi: 10.2174/0115701611308960241014155413.
Diabetic foot ulcers (DFUs) pose a significant clinical challenge, characterized by impaired wound healing, chronic inflammation, and increased risk of infection. Neutrophils, as critical components of the innate immune response, play a pivotal role in the initial stages of wound healing, particularly during the inflammatory phase. This review explores the intricate relationship between neutrophil migration, inflammation, and the pathogenesis of DFU and drugs that can impact neutrophil production and migration. Neutrophils contribute to infection control through phagocytosis and release pro-inflammatory cytokines and reactive oxygen species, which, when dysregulated, can impede the wound healing process. Furthermore, the chronic hyperglycemic state characteristic of diabetes mellitus has been implicated in impairing neutrophil functions, including chemotaxis and oxidative burst. This compromised neutrophil response prolongs the inflammatory phase and disrupts the delicate balance required for efficient wound healing. Neutrophil extracellular traps (NETs), a unique form of neutrophil defence, have also been implicated in DFU pathogenesis, potentially exacerbating inflammation and tissue damage. Understanding the intricate interplay between neutrophil migration, dysregulated inflammatory responses, and hyperglycemia-driven impairments is essential for developing targeted therapeutic strategies for DFUs. This review sheds light on the critical role of neutrophils in DFU pathogenesis, and innovative and advanced treatment strategies for DFU, highlighting the potential for novel interventions to restore the balance between pro-inflammatory and wound healing processes, ultimately improving clinical outcomes for individuals with DFU.
糖尿病足溃疡（DFU）构成了重大的临床挑战，其特征为伤口愈合受损、慢性炎症以及感染风险增加。中性粒细胞作为先天性免疫反应的关键组成部分，在伤口愈合的初始阶段，特别是在炎症期发挥着关键作用。本综述探讨了中性粒细胞迁移、炎症与DFU发病机制之间的复杂关系，以及能够影响中性粒细胞生成和迁移的药物。中性粒细胞通过吞噬作用以及释放促炎细胞因子和活性氧来控制感染，然而，当这些过程失调时，会阻碍伤口愈合进程。此外，糖尿病特有的慢性高血糖状态与中性粒细胞功能受损有关，包括趋化性和氧化爆发。这种受损的中性粒细胞反应会延长炎症期，并破坏有效伤口愈合所需的微妙平衡。中性粒细胞胞外陷阱（NETs）作为中性粒细胞防御的一种独特形式，也与DFU发病机制有关，可能会加剧炎症和组织损伤。了解中性粒细胞迁移、失调的炎症反应以及高血糖驱动的损伤之间的复杂相互作用，对于制定DFU的靶向治疗策略至关重要。本综述揭示了中性粒细胞在DFU发病机制中的关键作用，以及DFU的创新和先进治疗策略，强调了新型干预措施恢复促炎和伤口愈合过程之间平衡的潜力，最终改善DFU患者的临床结局。
