JIN431055.indd E-Mail karger@karger.com Editorial J Innate Immun 2015;7:555–556 DOI: 10.1159/000431055 The Neutrophil: A Beautiful Beast or a Beastly Beauty? phenotype are not known. In this issue, Sawant et al. [9] present highly interesting data showing that CXCL1 monomer-dimer distribution and receptor interactions are highly coupled and regulate neutrophil trafficking, and that injury in the context of disease is a consequence of inappropriate CXCR2 activation at the target tissue [10] . The classic view is that neutrophils are important in bacterial killing [11] . However, they can also recognize damage-associated molecular patterns (DAMPs) during tissue-damage and participate in viral host defense [12, 13] . Another important function is the formation of neu- trophil extracellular traps (NETs), formed during an ac- tive cellular process where the neutrophil releases its DNA to the extracellular environment [14, 15] . Finally, resolution of neutrophil inflammation has to be tightly regulated to avoid accumulation of these cells, as is exem- plified by the prolonged and excessive inflammation in cystic fibrosis [16–18] . The rapidly increasing knowledge regarding the im- munobiology of this fascinating and important cell should attract the attention of a broad readership interested in innate immunity. Heiko Herwald , Lund Arne Egesten , Lund Neutrophils are crucial to keeping us in a healthy state, but they also play important roles in the pathophysiology of a broad spectrum of diseases [1] . Early on, they were regarded as quite primitive cells, simply executing cyto- toxic functions. It has become evident, however, that they are highly sophisticated and can perform complex func- tions in many inflammatory contexts. Neutrophils origi- nate from stem cells in the bone marrow where growth factors induce sequential expression of genes, resulting in a distinct phenotype, not least characterized by its differ- ent sets of cytoplasmic granule containing preformed host defense proteins ready to be released at sites of in- flammation [1] . Being transported in the bloodstream, specific adhesion molecules expressed by endothelial cells and chemotactic gradients are important for neutrophil recruitment and activation [2–5] . ELR-positive CXC chemokines, including IL-8/ CXCL8, are important during this process. Interestingly, there are two receptors for this group of ligands with varying affinities [6–8] . CXCL1 mediates neutrophil re- cruitment by binding and activating CXCR2, and inhibi- tion of this receptor shows that dysregulation of CXCL1/ CXCR2 function is correlated with the severity of disease [9] . However, the mechanisms that turn the beneficial CXCL1-mediated neutrophil functions into a destructive Published online: September 8, 2015 Journal of Innate Immunity © 2015 S. Karger AG, Basel 1662–811X/15/0076–0555$39.50/0 www.karger.com/jin Herwald/Egesten J Innate Immun 2015;7:555–556 DOI: 10.1159/000431055 556 References 1 Nauseef WM, Borregaard N: Neutrophils at work. Nat Immunol 2014; 15: 602–611. 2 Daniel AE, van Buul JD: Endothelial junct- ion regulation: a prerequisite for leukocytes crossing the vessel wall. J Innate Immun 2013; 5: 324–335. 3 Grommes J, Drechsler M, Soehnlein O: CCR5 and FPR1 mediate neutrophil recruitment in endotoxin-induced lung injury. J Innate Im- mun 2014; 6: 111–116. 4 Rossaint J, Zarbock A: Tissue-specific neutro- phil recruitment into the lung, liver, and kid- ney. J Innate Immun 2013; 5: 348–357. 5 Herter JM, Rossaint J, Spieker T, Zarbock A: Adhesion molecules involved in neutrophil recruitment during sepsis-induced acute kid- ney injury. J Innate Immun 2014; 6: 597–606. 6 Murphy PM, Tiffany HL: Cloning of comple- mentary DNA encoding a functional human interleukin-8 receptor. Science 1991; 253: 1280–1283. 7 Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI: Structure and functional expres- sion of a human interleukin-8 receptor. Sci- ence 1991; 253: 1278–1280. 8 Moser B, Schumacher C, von Tscharner V, Clark-Lewis I, Baggiolini M: Neutrophil-acti- vating peptide 2 and gro/melanoma growth- stimulatory activity interact with neutrophil- activating peptide 1/interleukin 8 receptors on human neutrophils. J Biol Chem 1991; 266: 10666–10671. 9 Sawant KV, Xu R, Cox R, Hawkins H, Sbrana E, Kolli D, Garofalo RP, Rajarathnam K: Che- mokine CXCL1-mediated neutrophil traf- ficking in the lung: role of CXCR2 activation. J Innate Immun 2015; 7: 647–658. 10 Nagarkar DR, Wang Q, Shim J, Zhao Y, Tsai WC, Lukacs NW, Sajjan U, Hershenson MB: CXCR2 is required for neutrophilic airway in- flammation and hyperresponsiveness in a mouse model of human rhinovirus infection. J Immunol 2009; 183: 6698–6707. 11 Lu T, Porter AR, Kennedy AD, Kobayashi SD, DeLeo FR: Phagocytosis and killing of Staph- ylococcus aureus by human neutrophils. J In- nate Immun 2014; 6: 639–649. 12 Pittman K, Kubes P: Damage-associated mo- lecular patterns control neutrophil recruit- ment. J Innate Immun 2013; 5: 315–323. 13 Casulli S, Elbim C: Interactions between hu- man immunodeficiency virus type 1 and polymorphonuclear neutrophils. J Innate Im- mun 2014; 6: 13–20. 14 Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A: Neutrophil extracellular traps kill bacteria. Science 2004; 303: 1532– 1535. 15 Braian C, Hogea V, Stendahl O: Mycobacte- rium tuberculosis -induced neutrophil extra- cellular traps activate human macrophages. J Innate Immun 2013; 5: 591–602. 16 Christenson K, Björkman L, Karlsson A, By- lund J: Regulation of neutrophil apoptosis dif- fers after in vivo transmigration to skin cham- bers and synovial fluid: a role for inflamma- some-dependent interleukin-1β release. J Innate Immun 2013; 5: 377–388. 17 Dwyer M, Shan Q, D’Ortona S, Maurer R, Mitchell R, Olesen H, Thiel S, Huebner J, Gadjeva M: Cystic fibrosis sputum DNA has NETosis characteristics and neutrophil extra- cellular trap release is regulated by macro- phage migration-inhibitory factor. J Innate Immun 2014; 6: 765–779. 18 Strydom N, Rankin SM: Regulation of circu- lating neutrophil numbers under homeostasis and in disease. J Innate Immun 2013; 5: 304– 314.