Neutrophils as effectors of vascular inflammation

Abstract

Vascular inflammation underlies most forms of cardiovascular disease, which remains a prevalent cause of death among the global population. Advances in the biology of neutrophils, as well as insights into their dynamics in tissues, have revealed that these cells are prominent drivers of vascular inflammation though derailed activation within blood vessels. The development of powerful imaging techniques, as well as identification of cells and molecules that regulate their activation within vessels, including platelets and catecholamines, has been instrumental to better understand the mechanisms through which neutrophils protect or damage the organism. Other advances in our understanding of how these leucocytes exert detrimental functions on neighbouring cells, including the formation of DNA-based extracellular traps, constitute milestones in defining neutrophil-driven inflammation. Here, we review emerging mechanisms that regulate intravascular activation and effector functions of neutrophils, and discuss specific pathologies in which these processes are relevant. We argue that identification of pathways and mechanisms specifically engaged within the vasculature may provide effective therapies to treat this prevalent group of pathologies.

Proteoglycan 4: From Mere Lubricant to Regulator of Tissue Homeostasis and Inflammation

“…Presence of sialylated and sulfated structures on mucin domain of PRG4 is assumed to contain epitopes that interact with L‐selectin . This result is both consistent and essential for our hypothesis as neutrophils are among the first responders to sites of inflammation . The migration of neutrophils from the circulation to the site of inflammation is controlled by interaction with the vascular epithelium and L‐selectin has been demonstrated to be essential for neutrophils to roll along the endothelium in the initiation phase of the adhesion cascade .…”

Tricuspid regurgitation velocity and other biomarkers of mortality in children, adolescents and young adults with sickle cell disease in the United States: The PUSH study

“…In SCD, intravascular hemolysis, free heme, inflammation and ischemia‐reperfusion injury accelerate neutrophil activation and binding to red bloods, platelets and endothelium 50‐52 . Neutrophil activation is believed to play an important role in vaso‐occlusive crisis 53 .…”

Circadian Features of Neutrophil Biology

“…The remarkably short lifespan of neutrophils in blood implies that many resources must be employed in their production (54). This feature likely relates to evolutionary trade-offs for a cell that is key to immune defense, but is also highly cytotoxic and can incite vascular inflammation (55). A consequence of this rapid turnover is that neutrophil numbers follow strong circadian changes in blood.…”