Priming of the neutrophil respiratory burst: role in host defense and inflammation

Abstract

Neutrophils are the major circulating white blood cells in humans. They play an essential role in host defense against pathogens. In healthy individuals, circulating neutrophils are in a dormant state with very low efficiency of capture and arrest on the quiescent endothelium. Upon infection and subsequent release of pro-inflammatory mediators, the vascular endothelium signals to circulating neutrophils to roll, adhere, and cross the endothelial barrier. Neutrophils migrate toward the infection site along a gradient of chemo-attractants, then recognize and engulf the pathogen. To kill this pathogen entrapped inside the vacuole, neutrophils produce and release high quantities of antibacterial peptides, proteases, and reactive oxygen species (ROS). The robust ROS production is also called 'the respiratory burst', and the NADPH oxidase or NOX2 is the enzyme responsible for the production of superoxide anion, leading to other ROS. In vitro, several soluble and particulate agonists induce neutrophil ROS production. This process can be enhanced by prior neutrophil treatment with 'priming' agents, which alone do not induce a respiratory burst. In this review, we will describe the priming process and discuss the beneficial role of controlled neutrophil priming in host defense and the detrimental effect of excessive neutrophil priming in inflammatory diseases.

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

“…Priming agents (e.g. fMLF, TNF-α) of bacterial and host origin serve to pre-activate or 'prime' neutrophils to form a more robust response upon encounter with a secondary stimulus (190). In the context of disease, primed neutrophils can be critical to ensuring a robust effective killing response, however an excessive priming can lead to unnecessary collateral host tissue damage.…”

“…Neutrophil priming is a pre-activation stage, where neutrophils are not fully active, but will become activated upon encountering a secondary stimulus (190). Once neutrophils are primed, they will induce an enhanced response to a secondary stimulus (284).…”

“…TNF-α, fMLF) and in vivo (e.g. GM-CSF, LPS, IL-8) turn on activation pathways without starting the activation process and they function to enhance fMLFinduced ROS production (190). In the primed state, the NADPH oxidase begins to undergo a preactivation process which includes protein redistribution, partial phosphorylation of the cytosolic component, p47 phox , as well as conformational changes; the activated state requires assembly of the complex (190).…”

“…GM-CSF, LPS, IL-8) turn on activation pathways without starting the activation process and they function to enhance fMLFinduced ROS production (190). In the primed state, the NADPH oxidase begins to undergo a preactivation process which includes protein redistribution, partial phosphorylation of the cytosolic component, p47 phox , as well as conformational changes; the activated state requires assembly of the complex (190). As observed in studies with LPS treatment of neutrophils, it enhances NADPH oxidase assembly and activation at the plasma membrane and simultaneously there is a pre-assembly of the neutrophil granules to the plasma membrane, which serves to pre-activate neutrophils (285).…”

“…As observed in studies with LPS treatment of neutrophils, it enhances NADPH oxidase assembly and activation at the plasma membrane and simultaneously there is a pre-assembly of the neutrophil granules to the plasma membrane, which serves to pre-activate neutrophils (285). A regulated priming response induced by host-or bacterial-derived factors presents an effective immune surveillance mechanism that promotes host defense; however, an excessive priming response results in an excessive production of ROS, leading to host tissue damage (190).…”