Neutrophils in Inflammatory Diseases: Unraveling the Impact of Their Derived Molecules and Heterogeneity

Abstract

Inflammatory diseases involve numerous disorders and medical conditions defined by an insufficient level of self-tolerance. These diseases evolve over the course of a multi-step process through which environmental variables play a crucial role in the emergence of aberrant innate and adaptive immunological responses. According to experimental data accumulated over the past decade, neutrophils play a significant role as effector cells in innate immunity. However, neutrophils are also involved in the progression of numerous diseases through participation in the onset and maintenance of immune-mediated dysregulation by releasing neutrophil-derived molecules and forming neutrophil extracellular traps, ultimately causing destruction of tissues. Additionally, neutrophils have a wide variety of functional heterogeneity with adverse effects on inflammatory diseases. However, the complicated role of neutrophil biology and its heterogeneity in inflammatory diseases remains unclear. Moreover, neutrophils are considered an intriguing target of interventional therapies due to their multifaceted role in a number of diseases. Several approaches have been developed to therapeutically target neutrophils, involving strategies to improve neutrophil function, with various compounds and inhibitors currently undergoing clinical trials, although challenges and contradictions in the field persist. This review outlines the current literature on roles of neutrophils, neutrophil-derived molecules, and neutrophil heterogeneity in the pathogenesis of autoimmune and inflammatory diseases with potential future therapeutic strategies.

Plants from Arid and Semi-Arid Zones of Mexico Used to Treat Respiratory Diseases: A Review

“…In a process of microbial infection or oxidative stress, defense cells are activated, also the synthesis of pro-inflammatory cells such as macrophages, interleukins, neutrophils from the MAPK metabolic pathway, which helps to inhibit pathogens. However, exposure of these cells to ROS leads to their lysis and degranulation, resulting in an increase in ROS level [ 131 ]. At this point, an important factor of protection is antioxidants from medicinal plants, which can inhibit ROS.…”

Fucoidan as a Promising Drug for Pain Treatment: Systematic Review and Meta-Analysis

“…The neutrophil is the first immune cell to respond to tissue damage or a potential aggressor [1]; in response to an injury, it migrates massively to the inflammatory focus, being clearly the most abundant cell [2]. Its role there is fundamental: on the one hand, thanks to its phagocytic capacity, it allows for the clearance of cellular debris associated with tissue damage and pathogens, along with degranulation and the release of nuclear material in the form of neutrophil extracellular traps (NETs), which also promote this process; on the other hand, it has the ability to release pro-inflammatory signaling molecules (mainly cytokines) that "call" other cells, favoring and accelerating their activation and migration to the affected area [3][4][5]. It can also sensitize sensory neurons, promoting their discharge [6,7].…”