Abstract
Neutrophils are first-line responders of the innate immune system. Following myocardial infarction (MI), neutrophils are quickly recruited to the ischemic region, where they initiate the inflammatory response, aiming at cleaning up dead cell debris. However, excessive accumulation and/or delayed removal of neutrophils are deleterious. Neutrophils can promote myocardial injury by releasing reactive oxygen species, granular components, and pro-inflammatory mediators. More recent studies have revealed that neutrophils are able to form extracellular traps (NETs) and produce extracellular vesicles (EVs) to aggravate inflammation and cardiac injury. On the contrary, there is growing evidence showing that neutrophils also exert anti-inflammatory, pro-angiogenic, and pro-reparative effects, thus facilitating inflammation resolution and cardiac repair. In this review, we summarize the current knowledge on neutrophils’ detrimental roles, highlighting the role of recently recognized NETs and EVs, followed by a discussion of their beneficial effects and molecular mechanisms in post-MI cardiac remodeling. In addition, emerging concepts about neutrophil diversity and their modulation of adaptive immunity are discussed.
Highlights
CXCL12-CXCR4 signaling is a retention signal that prevents neutrophil egress from the bone marrow, while the CXCL1/2-CXCR2 signal drives their mobilization into the peripheral blood [3,4,5]
In steady-state conditions, neutrophil production is tightly regulated by granulocyte colony stimulating factor (G-CSF), a cytokine primarily secreted by immune cells, including neutrophils [68]
Disruption of S100A8/A9 and downstream signaling cascade inhibit myocardial infarction (MI)-induced granulopoiesis and alleviate cardiac dysfunction [71]. This is in line with previous work revealing that S100A8/A9 blockade reduces neutrophil production and infiltration into the myocardium, as well as improves cardiac function after MI [72,73]
Summary
Neutrophils are the most abundant circulating leukocytes in humans and act as the first responders to infection and sterile inflammation. A recent study using neutrophil reporter mice showed that in the steady state, neutrophils actively infiltrate most tissues, including the heart [6]. Their lifespan in most tissues is one day or less [7]. Blood neutrophils infiltrate the ischemic myocardium in large quantities, within a few hours after MI onset [9,10] They are attracted by cell debris and inflammatory mediators released by activated resident cells. Recruited neutrophils initially aim to phagocytose and clear dead cell debris caused by ischemia They concomitantly cause collateral cardiac injury by releasing reactive oxygen species (ROS), proteolytic enzymes, and inflammatory mediators [14,15]. We discuss the emerging concept about neutrophil diversity and their regulation of an adaptive immune response
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
