ReviewRole of polymorphonuclear neutrophils in atherosclerosis: Current state and future perspectives
Section snippets
Neutrophils as key component of the inflammatory response
PMN are known to play important roles in inflammation by virtue of their ability to perform a series of effector functions that collectively represent a major mechanism of innate immunity [9]. Most of these functions are dependent on the mobilization of cytoplasmic granules and secretory vesicles, which constitute an important reservoir not only of antimicrobial proteins, proteases, and components of the respiratory burst oxidase, but also of a wide variety of membrane-bound receptors for
Neutrophils in experimental animal models of atherosclerosis and arterial injury
The systematic investigation on the mechanisms that initiate atherosclerosis and mediate its clinical manifestation relies on animal models of the disease [2], [22]. Neutrophils are the first leukocytes to infiltrate inflamed tissues. An early influx of neutrophils has been described in several experimental models of vascular injury, including endotoxin-induced injury [23], air drying [24], transmural electrical stimulation [25], transluminal wire injury [26], perivascular collar placement [27]
Neutrophils in human atherosclerosis and its cardiovascular complications
Several lines of evidence suggest that neutrophils can play a pivotal role in human atherosclerosis (Table 3). A number of observational epidemiologic studies over more than two decades have documented a relationship between an elevated circulating white blood cell (WBC) count and increased cardiovascular risk [37], [38]. Importantly, among the different WBC subtypes, a greater predictive ability was found to be provided by high PMN count [39], [40], [41], [42], [43], [44]. In line with these
Pharmacological modulation of neutrophil functions in atherosclerosis
PMN recruitment into inflamed tissue proceeds in a cascade-like fashion. The first contact of neutrophils with the endothelium is mediated by selectins and their cognate receptors, followed by rolling of neutrophils along the endothelial wall and integrin-mediated arrest; while rolling, neutrophils collect different inflammatory signals that can activate several pathways, such as selectin- and selectin ligand-induced signaling, chemoattractant-induced G-protein-coupled receptor (GPCR)
Concluding remarks
The past decade has witnessed a remarkable increase in our understanding of the importance of inflammation in all stages of atherosclerotic disease. PMN are ubiquitous effector cells in inflammatory conditions, but their role in human atherosclerosis has long been neglected. Despite this drawback, it has become evident that PMN, the first leukocytes to infiltrate the inflamed tissue, have the potential of making important contributions to vascular inflammatory processes driving the development
Acknowledgements
We thank Dr. E. Donetti (University of Milan, Italy) for kindly providing transmission electron microscopy images of PMN emperipolesis by SMC, and the Reviewers for improving the clarity of this article.
R.B. was supported by a grant from the Fondo per gli Investimenti della Ricerca di Base (FIRB) CHEM-PROFARMA-NET.
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