TY - JOUR T1 - Red, amber and green: the role of the lung in de-priming active systemic neutrophils JF - Thorax JO - Thorax SP - 606 LP - 608 DO - 10.1136/thoraxjnl-2014-205438 VL - 69 IS - 7 AU - Sapey, Elizabeth AU - Stockley, Robert A Y1 - 2014/07/01 UR - http://thorax.bmj.com/content/69/7/606.abstract N2 - There is little doubt that neutrophils, while vital in host defence, have the potential to cause significant tissue damage implicated both in lung and systemic diseases as well as systemic organ failure. Following pathogen recognition receptor activation by agents including formyl-methionyl-leucyl-phenylalanine (fMLP), cigarette smoke, cytokines or complement factor C5a, neutrophils are activated, recruited and participate in tissue breakdown and bacterial clearance via an array of mechanisms including phagocytosis, superoxide burst, extrusion of neutrophil extracellular traps (de-condensed chromatin and antimicrobial protein coated web-like structures), secretion of reactive oxygen and nitrogen species, and extrusion of a range of granule-derived proteases and antimicrobial peptides. These proteases, hydrolases and antimicrobial peptides are thought to contribute to many cellular functions including neutrophil migration, adherence and apoptosis, but their extra-cellular release is also associated with obligate tissue damage (as described in studies of quantum proteolysis1) and inflammation, and neutrophil proteinases in particular have been found to have a myriad of pro-inflammatory effects on bystander tissue to amplify inflammation, favouring further cell recruitment and degranulation.In keeping with this, there are clear associations between neutrophils and many chronic inflammatory diseases as diverse as COPD, myocardial infarction, type 2 diabetes and inflammatory bowel disease.2 Neutrophils have also been implicated widely in organ dysfunction, from acute kidney injury to acute lung injury, where neutrophil numbers correlate both with the severity of insult and negative outcomes.3 Neutrophils exist in one of three states: quiescent, primed or active. Priming and activation appear distinct. In the primed state, there is no increase in oxidase activity; however, subsequent stimulation is able to provoke a response that is 10-fold larger than in non-primed, activated cells. Individual primed cells are ‘ready to go’ but require further stimulation before activated responses are elicited. This is akin to a tri-colour warning system, with primed … ER -