Skip to main content

Advertisement

SpringerLink
Log in

Neutrophil chemotaxis

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Neutrophils are the primary cells recruited to inflamed sites during an innate immune response to tissue damage and/or infection. They are finely sensitive to inciting stimuli to reach in great numbers and within minutes areas of inflammation and tissue insult. For this effective response, they can detect extracellular chemical gradients and move towards higher concentrations, the so-called chemotaxis process or guided cell migration. This directed neutrophil recruitment is orchestrated by chemoattractants, a chemically diverse group of molecular guidance cues (e.g., lipids, N-formylated peptides, complement, anaphylotoxins and chemokines). Neutrophils respond to these guidance signals in a hierarchical manner and, based on this concept, they can be further subdivided into two groups: “end target” and “intermediary” chemoattractants, the signals of the former dominant over the latter. Neutrophil chemoattractants exert their effects through interaction with heptahelical G protein-coupled receptors (GPCRs) expressed on cell surfaces and the chemotactic response is mainly regulated by the Rho family of GTPases. Additionally, neutrophil behavior might differ and be affected in different complex scenarios such as disease conditions and type of vascular bed in specific organs. Finally, there are different mechanisms to disrupt neutrophil chemotaxis either associated to the resolution of inflammation or to bacterial escape and systemic infection. Therefore, in the present review, we will discuss the different molecular players involved in neutrophil chemotaxis, paying special attention to the different chemoattractants described and the way that they interact intra- and extravascularly for neutrophils to properly reach the target tissue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Afonso PV, Janka-Junttila M, Lee YJ, McCann CP, Oliver CM, Aamer KA, Losert W, Cicerone MT, Parent CA (2012) LTB4 is a signal-relay molecule during neutrophil chemotaxis. Dev Cell 22:1079–1091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aherne CM, Collins CB, Masterson JC, Tizzano M, Boyle TA, Westrich JA, Parnes JA, Furuta GT, Rivera-Nieves J, Eltzschig HK (2012) Neuronal guidance molecule netrin-1 attenuates inflammatory cell trafficking during acute experimental colitis. Gut 61:695–705

    Article  CAS  PubMed  Google Scholar 

  • Allendorf DJ, Yan J, Ross GD, Hansen RD, Baran JT, Subbarao K, Wang L, Haribabu B (2005) C5a-mediated leukotriene B4-amplified neutrophil chemotaxis is essential in tumor immunotherapy facilitated by anti-tumor monoclonal antibody and beta-glucan. J Immunol 174:7050–7056

    Article  CAS  PubMed  Google Scholar 

  • Alves-Filho JC, Freitas A, Souto FO, Spiller F, Paula-Neto H, Silva JS, Gazzinelli RT, Teixeira MM, Ferreira SH, Cunha FQ (2009) Regulation of chemokine receptor by toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis. Proc Natl Acad Sci U S A 106:4018–4023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alves-Filho JC, Sonego F, Souto FO, Freitas A, Verri WA Jr, Auxiliadora-Martins M, Basile-Filho A, McKenzie AN, Xu D, Cunha FQ, Liew FY (2010) Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med 16:708–712

    Article  CAS  PubMed  Google Scholar 

  • Baggiolini M (2001) Chemokines in pathology and medicine. J Intern Med 250:91–104

    Article  CAS  PubMed  Google Scholar 

  • Barletta KE, Ley K, Mehrad B (2012) Regulation of neutrophil function by adenosine. Arterioscler Thromb Vasc Biol 32:856–864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beyrau M, Bodkin JV, Nourshargh S (2012) Neutrophil heterogeneity in health and disease: a revitalized avenue in inflammation and immunity. Open Biol 2:120134

    Article  PubMed  PubMed Central  Google Scholar 

  • Cara DC, Kaur J, Forster M, McCafferty DM, Kubes P (2001) Role of p38 mitogen-activated protein kinase in chemokine-induced emigration and chemotaxis in vivo. J Immunol 167:6552–6558

    Article  CAS  PubMed  Google Scholar 

  • Cheung YY, Kim SY, Yiu WH, Pan CJ, Jun HS, Ruef RA, Lee EJ, Westphal H, Mansfield BC, Chou JY (2007) Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta. J Clin Invest 117:784–793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chou RC, Kim ND, Sadik CD, Seung E, Lan Y, Byrne MH, Haribabu B, Iwakura Y, Luster AD (2010) Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis. Immunity 33:266–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colom B, Bodkin JV, Beyrau M, Woodfin A, Ody C, Rourke C, Chavakis T, Brohi K, Imhof BA, Nourshargh S (2015) Leukotriene B4-Neutrophil Elastase Axis drives Neutrophil reverse Transendothelial cell migration in vivo. Immunity 42:1075–1086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corriden R, Insel PA (2012) New insights regarding the regulation of chemotaxis by nucleotides, adenosine, and their receptors. Purinergic Signal 8:587–598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dahlgren C, Gabl M, Holdfeldt A, Winther M, Forsman H (2016) Basic characteristics of the neutrophil receptors that recognize formylated peptides, a danger-associated molecular pattern generated by bacteria and mitochondria. Biochem Pharmacol 114:22–39

    Article  CAS  PubMed  Google Scholar 

  • de la Fuente H, Richaud-Patin Y, Jakez-Ocampo J, Gonzalez-Amaro R, Llorente L (2001) Innate immune mechanisms in the pathogenesis of systemic lupus erythematosus (SLE). Immunol Lett 77:175–180

    Article  PubMed  Google Scholar 

  • de Oliveira S, Rosowski EE, Huttenlocher A (2016) Neutrophil migration in infection and wound repair: going forward in reverse. Nat Rev Immunol 16:378–391

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dixit N, Yamayoshi I, Nazarian A, Simon SI (2011) Migrational guidance of neutrophils is mechanotransduced via high-affinity LFA-1 and calcium flux. J Immunol 187:472–481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB (2011) Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet J Rare Dis 6:26

    Article  PubMed  PubMed Central  Google Scholar 

  • Edwards LJ, Constantinescu CS (2009) Platelet activating factor/platelet activating factor receptor pathway as a potential therapeutic target in autoimmune diseases. Inflamm Allergy Drug Targets 8:182–190

    Article  CAS  PubMed  Google Scholar 

  • Fayngerts SA, Wang Z, Zamani A, Sun H, Boggs AE, Porturas TP, Xie W, Lin M, Cathopoulis T, Goldsmith JR, Vourekas A, Chen YH (2017) Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2. Nat Immunol 18:1353–1360

    Article  CAS  PubMed  Google Scholar 

  • Fine N, Dimitriou ID, Rullo J, Sandi MJ, Petri B, Haitsma J, Ibrahim H, La Rose J, Glogauer M, Kubes P, Cybulsky M, Rottapel R (2016) GEF-H1 is necessary for neutrophil shear stress-induced migration during inflammation. J Cell Biol 215:107–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Firatli E, Tuzun B, Efeoglu A (1996) Papillon-Lefevre syndrome. Analysis of Neutrophil Chemotaxis. J Periodontol 67:617–620

    Article  CAS  PubMed  Google Scholar 

  • Friedl P, Weigelin B (2008) Interstitial leukocyte migration and immune function. Nat Immunol 9:960–969

    Article  CAS  PubMed  Google Scholar 

  • Gallin JI (1984) Human neutrophil heterogeneity exists, but is it meaningful? Blood 63:977–983

    CAS  PubMed  Google Scholar 

  • Gerin I, Veiga-da-Cunha M, Achouri Y, Collet JF, Van Schaftingen E (1997) Sequence of a putative glucose 6-phosphate translocase, mutated in glycogen storage disease type Ib. FEBS Lett 419:235–238

    Article  CAS  PubMed  Google Scholar 

  • Ghasemzadeh M, Hosseini E (2015) Intravascular leukocyte migration through platelet thrombi: directing leukocytes to sites of vascular injury. Thromb Haemost 113:1224–1235

    Article  PubMed  Google Scholar 

  • Handel TM, Johnson Z, Crown SE, Lau EK, Proudfoot AE (2005) Regulation of protein function by glycosaminoglycans--as exemplified by chemokines. Annu Rev Biochem 74:385–410

    Article  CAS  PubMed  Google Scholar 

  • Haneke E (1979) The Papillon-Lefevre syndrome: keratosis palmoplantaris with periodontopathy. Report of a case and review of the cases in the literature. Hum Genet 51:1–35

    Article  CAS  PubMed  Google Scholar 

  • Harayama T, Shindou H, Ogasawara R, Suwabe A, Shimizu T (2008) Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor. J Biol Chem 283:11097–11106

    Article  CAS  PubMed  Google Scholar 

  • Harding MG, Zhang K, Conly J, Kubes P (2014) Neutrophil crawling in capillaries; a novel immune response to Staphylococcus aureus. PLoS Pathog 10:e1004379

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Headland SE, Norling LV (2015) The resolution of inflammation: principles and challenges. Semin Immunol 27:149–160

    Article  CAS  PubMed  Google Scholar 

  • Heit B, Robbins SM, Downey CM, Guan Z, Colarusso P, Miller BJ, Jirik FR, Kubes P (2008) PTEN functions to ‘prioritize’ chemotactic cues and prevent ‘distraction’ in migrating neutrophils. Nat Immunol 9:743–752

    Article  CAS  PubMed  Google Scholar 

  • Heit B, Tavener S, Raharjo E, Kubes P (2002) An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients. J Cell Biol 159:91–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hepper I, Schymeinsky J, Weckbach LT, Jakob SM, Frommhold D, Sixt M, Laschinger M, Sperandio M, Walzog B (2012) The mammalian actin-binding protein 1 is critical for spreading and intraluminal crawling of neutrophils under flow conditions. J Immunol 188:4590–4601

    Article  CAS  PubMed  Google Scholar 

  • Herlihy SE, Brown ML, Pilling D, Weeks BR, Myers LK, Gomer RH (2015) Role of the neutrophil chemorepellent soluble dipeptidyl peptidase IV in decreasing inflammation in a murine model of arthritis. Arthritis Rheumatol 67:2634–2638

    Article  PubMed  PubMed Central  Google Scholar 

  • Herlihy SE, Pilling D, Maharjan AS, Gomer RH (2013) Dipeptidyl peptidase IV is a human and murine neutrophil chemorepellent. J Immunol 190:6468–6477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herrmann JM, Bernardo J, Long HJ, Seetoo K, McMenamin ME, Batista EL Jr, Van Dyke TE, Simons ER (2007) Sequential chemotactic and phagocytic activation of human polymorphonuclear neutrophils. Infect Immun 75:3989–3998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herter JM, Rossaint J, Block H, Welch H, Zarbock A (2013) Integrin activation by P-Rex1 is required for selectin-mediated slow leukocyte rolling and intravascular crawling. Blood 121:2301–2310

    Article  CAS  PubMed  Google Scholar 

  • Hillyer P, Male D (2005) Expression of chemokines on the surface of different human endothelia. Immunol Cell Biol 83:375–382

    Article  CAS  PubMed  Google Scholar 

  • Huang C, Jacobson K, Schaller MD (2004) MAP kinases and cell migration. J Cell Sci 117:4619–4628

    Article  CAS  PubMed  Google Scholar 

  • Iglesias PA, Devreotes PN (2008) Navigating through models of chemotaxis. Curr Opin Cell Biol 20:35–40

    Article  CAS  PubMed  Google Scholar 

  • Ishii M, Asano K, Namkoong H, Tasaka S, Mizoguchi K, Asami T, Kamata H, Kimizuka Y, Fujiwara H, Funatsu Y, Kagawa S, Miyata J, Ishii K, Nakamura M, Hirai H, Nagata K, Kunkel SL, Hasegawa N, Betsuyaku T (2012) CRTH2 is a critical regulator of neutrophil migration and resistance to polymicrobial sepsis. J Immunol 188:5655–5664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson GL, Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298:1911–1912

    Article  CAS  PubMed  Google Scholar 

  • Johnston B, Burns AR, Suematsu M, Issekutz TB, Woodman RC, Kubes P (1999) Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1. J Clin Invest 103:1269–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jorizzo JL, Hudson RD, Schmalstieg FC, Daniels JC, Apisarnthanarax P, Henry JC, Gonzalez EB, Ichikawa Y, Cavallo T (1984) Behcet’s syndrome: immune regulation, circulating immune complexes, neutrophil migration, and colchicine therapy. J Am Acad Dermatol 10:205–214

    Article  CAS  PubMed  Google Scholar 

  • Jun HS, Weinstein DA, Lee YM, Mansfield BC, Chou JY (2014) Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type Ib. Blood 123:2843–2853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keszei M, Westerberg LS (2014) Congenital defects in neutrophil dynamics. J Immunol Res 2014:303782

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kumar AV, Katakam SK, Urbanowitz AK, Gotte M (2015) Heparan sulphate as a regulator of leukocyte recruitment in inflammation. Curr Protein Pept Sci 16:77–86

    Article  CAS  PubMed  Google Scholar 

  • Lacalle RA, Peregil RM, Albar JP, Merino E, Martinez AC, Merida I, Manes S (2007) Type I phosphatidylinositol 4-phosphate 5-kinase controls neutrophil polarity and directional movement. J Cell Biol 179:1539–1553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lammermann T, Bader BL, Monkley SJ, Worbs T, Wedlich-Soldner R, Hirsch K, Keller M, Forster R, Critchley DR, Fassler R, Sixt M (2008) Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 453:51–55

    Article  PubMed  CAS  Google Scholar 

  • Lehmann DM, Seneviratne AM, Smrcka AV (2008) Small molecule disruption of G protein beta gamma subunit signaling inhibits neutrophil chemotaxis and inflammation. Mol Pharmacol 73:410–418

    Article  CAS  PubMed  Google Scholar 

  • Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689

    Article  CAS  PubMed  Google Scholar 

  • Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM (2013) C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB J 27:855–864

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Dong X, Wang Z, Liu W, Deng N, Ding Y, Tang L, Hla T, Zeng R, Li L, Wu D (2005) Regulation of PTEN by Rho small GTPases. Nat Cell Biol 7:399–404

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Hannigan M, Mo Z, Liu B, Lu W, Wu Y, Smrcka AV, Wu G, Li L, Liu M, Huang CK, Wu D (2003) Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42. Cell 114:215–227

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Jiang H, Xie W, Zhang Z, Smrcka AV, Wu D (2000) Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction. Science 287:1046–1049

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Ma B, Malik AB, Tang H, Yang T, Sun B, Wang G, Minshall RD, Li Y, Zhao Y, Ye RD, Xu J (2012) Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases. Nat Immunol 13:457–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lokuta MA, Senetar MA, Bennin DA, Nuzzi PA, Chan KT, Ott VL, Huttenlocher A (2007) Type Igamma PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis. Mol Biol Cell 18:5069–5080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Majumdar R, Tavakoli Tameh A, Parent CA (2016) Exosomes mediate LTB4 release during Neutrophil Chemotaxis. PLoS Biol 14:e1002336

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Massena S, Christoffersson G, Hjertstrom E, Zcharia E, Vlodavsky I, Ausmees N, Rolny C, Li JP, Phillipson M (2010) A chemotactic gradient sequestered on endothelial heparan sulfate induces directional intraluminal crawling of neutrophils. Blood 116:1924–1931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathias JR, Perrin BJ, Liu TX, Kanki J, Look AT, Huttenlocher A (2006) Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish. J Leukoc Biol 80:1281–1288

    Article  CAS  PubMed  Google Scholar 

  • McDonald B, Kubes P (2011) Cellular and molecular choreography of neutrophil recruitment to sites of sterile inflammation. J Mol Med 89:1079–1088

    Article  CAS  PubMed  Google Scholar 

  • McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, Beck PL, Muruve DA, Kubes P (2010) Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330:362–366

    Article  CAS  PubMed  Google Scholar 

  • Middleton J, Patterson AM, Gardner L, Schmutz C, Ashton BA (2002) Leukocyte extravasation: chemokine transport and presentation by the endothelium. Blood 100:3853–3860

    Article  CAS  PubMed  Google Scholar 

  • Molad Y, Buyon J, Anderson DC, Abramson SB, Cronstein BN (1994) Intravascular neutrophil activation in systemic lupus erythematosus (SLE): dissociation between increased expression of CD11b/CD18 and diminished expression of L-selectin on neutrophils from patients with active SLE. Clin Immunol Immunopathol 71:281–286

    Article  CAS  PubMed  Google Scholar 

  • Movassagh H, Saati A, Nandagopal S, Mohammed A, Tatari N, Shan L, Duke-Cohan JS, Fowke KR, Lin F, Gounni AS (2017) Chemorepellent Semaphorin 3E negatively regulates Neutrophil migration in vitro and in vivo. J Immunol 198:1023–1033

    Article  CAS  PubMed  Google Scholar 

  • Narisawa K, Igarashi Y, Otomo H, Tada K (1978) A new variant of glycogen storage disease type I probably due to a defect in the glucose-6-phosphate transport system. Biochem Biophys Res Commun 83:1360–1364

    Article  CAS  PubMed  Google Scholar 

  • Neptune ER, Bourne HR (1997) Receptors induce chemotaxis by releasing the betagamma subunit of Gi, not by activating Gq or Gs. Proc Natl Acad Sci U S A 94:14489–14494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishio M, Watanabe K, Sasaki J, Taya C, Takasuga S, Iizuka R, Balla T, Yamazaki M, Watanabe H, Itoh R, Kuroda S, Horie Y, Forster I, Mak TW, Yonekawa H, Penninger JM, Kanaho Y, Suzuki A, Sasaki T (2007) Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1. Nat Cell Biol 9:36–44

    Article  CAS  PubMed  Google Scholar 

  • Nourshargh S, Alon R (2014) Leukocyte migration into inflamed tissues. Immunity 41:694–707

    Article  CAS  PubMed  Google Scholar 

  • Nourshargh S, Hordijk PL, Sixt M (2010) Breaching multiple barriers: leukocyte motility through venular walls and the interstitium. Nat Rev Mol Cell Biol 11:366–378

    Article  CAS  PubMed  Google Scholar 

  • Perretti M, Dalli J (2009) Exploiting the Annexin A1 pathway for the development of novel anti-inflammatory therapeutics. Br J Pharmacol 158:936–946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peters-Golden M, Henderson WR Jr (2007) Leukotrienes. N Engl J Med 357:1841–1854

    Article  CAS  PubMed  Google Scholar 

  • Petri B, Phillipson M, Kubes P (2008) The physiology of leukocyte recruitment: an in vivo perspective. J Immunol 180:6439–6446

    Article  CAS  PubMed  Google Scholar 

  • Phillipson M, Heit B, Colarusso P, Liu L, Ballantyne CM, Kubes P (2006) Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med 203:2569–2575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phillipson M, Heit B, Parsons SA, Petri B, Mullaly SC, Colarusso P, Gower RM, Neely G, Simon SI, Kubes P (2009) Vav1 is essential for mechanotactic crawling and migration of neutrophils out of the inflamed microvasculature. J Immunol 182:6870–6878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phillipson M, Kubes P (2011) The neutrophil in vascular inflammation. Nat Med 17:1381–1390

    Article  CAS  PubMed  Google Scholar 

  • Proebstl D, Voisin MB, Woodfin A, Whiteford J, D’Acquisto F, Jones GE, Rowe D, Nourshargh S (2012) Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med 209:1219–1234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pruenster M, Mudde L, Bombosi P, Dimitrova S, Zsak M, Middleton J, Richmond A, Graham GJ, Segerer S, Nibbs RJ, Rot A (2009) The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity. Nat Immunol 10:101–108

    Article  CAS  PubMed  Google Scholar 

  • Quinton LJ, Nelson S, Zhang P, Boe DM, Happel KI, Pan W, Bagby GJ (2004) Selective transport of cytokine-induced neutrophil chemoattractant from the lung to the blood facilitates pulmonary neutrophil recruitment. Am J Physiol Lung Cell Mol Physiol 286:L465–L472

    Article  CAS  PubMed  Google Scholar 

  • Raftopoulou M, Hall A (2004) Cell migration: Rho GTPases lead the way. Dev Biol 265:23–32

    Article  CAS  PubMed  Google Scholar 

  • Ram G, Chinen J (2011) Infections and immunodeficiency in down syndrome. Clin Exp Immunol 164:9–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR (2003) Cell migration: integrating signals from front to back. Science 302:1704–1709

    Article  CAS  PubMed  Google Scholar 

  • Rosenberger P, Schwab JM, Mirakaj V, Masekowsky E, Mager A, Morote-Garcia JC, Unertl K, Eltzschig HK (2009) Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia. Nat Immunol 10:195–202

    Article  CAS  PubMed  Google Scholar 

  • Sadik CD, Luster AD (2012) Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation. J Leukoc Biol 91:207–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanz MJ, Kubes P (2012) Neutrophil-active chemokines in in vivo imaging of neutrophil trafficking. Eur J Immunol 42:278–283

    Article  CAS  PubMed  Google Scholar 

  • Schaff UY, Dixit N, Procyk E, Yamayoshi I, Tse T, Simon SI (2010) Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow. Blood 115:657–666

    Article  PubMed  PubMed Central  Google Scholar 

  • Schmidt S, Moser M, Sperandio M (2013) The molecular basis of leukocyte recruitment and its deficiencies. Mol Immunol 55:49–58

    Article  CAS  PubMed  Google Scholar 

  • Serhan CN (2010) Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not? Am J Pathol 177:1576–1591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8:349–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shelef MA, Tauzin S, Huttenlocher A (2013) Neutrophil migration: moving from zebrafish models to human autoimmunity. Immunol Rev 256:269–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER (2010) Neutrophil kinetics in health and disease. Trends Immunol 31:318–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teng TS, Ji AL, Ji XY, Li YZ (2017) Neutrophils and immunity: from bactericidal action to being conquered. J Immunol Res 2017:9671604

    Article  PubMed  PubMed Central  Google Scholar 

  • Turner MD, Nedjai B, Hurst T, Pennington DJ (2014) Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta 1843:2563–2582

    Article  CAS  PubMed  Google Scholar 

  • Ulvmar MH, Hub E, Rot A (2011) Atypical chemokine receptors. Exp Cell Res 317:556–568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Voisin MB, Nourshargh S (2013) Neutrophil transmigration: emergence of an adhesive cascade within venular walls. J Innate Immun 5:336–347

    Article  CAS  PubMed  Google Scholar 

  • Voisin MB, Probstl D, Nourshargh S (2010) Venular basement membranes ubiquitously express matrix protein low-expression regions: characterization in multiple tissues and remodeling during inflammation. Am J Pathol 176:482–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Voisin MB, Woodfin A, Nourshargh S (2009) Monocytes and neutrophils exhibit both distinct and common mechanisms in penetrating the vascular basement membrane in vivo. Arterioscler Thromb Vasc Biol 29:1193–1199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang L, Fuster M, Sriramarao P, Esko JD (2005) Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses. Nat Immunol 6:902–910

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Voisin MB, Larbi KY, Dangerfield J, Scheiermann C, Tran M, Maxwell PH, Sorokin L, Nourshargh S (2006) Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med 203:1519–1532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weathington NM, van Houwelingen AH, Noerager BD, Jackson PL, Kraneveld AD, Galin FS, Folkerts G, Nijkamp FP, Blalock JE (2006) A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med 12:317–323

    Article  CAS  PubMed  Google Scholar 

  • Weiner OD (2002) Regulation of cell polarity during eukaryotic chemotaxis: the chemotactic compass. Curr Opin Cell Biol 14:196–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wojciak-Stothard B, Ridley AJ (2003) Shear stress-induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases. J Cell Biol 161:429–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong K, Van Keymeulen A, Bourne HR (2007) PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing neutrophil-like cells. J Cell Biol 179:1141–1148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodfin A, Voisin MB, Beyrau M, Colom B, Caille D, Diapouli FM, Nash GB, Chavakis T, Albelda SM, Rainger GE, Meda P, Imhof BA, Nourshargh S (2011) The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol 12:761–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodfin A, Voisin MB, Nourshargh S (2010) Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol 17:9–17

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu D (2005) Signaling mechanisms for regulation of chemotaxis. Cell Res 15:52–56

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Hannigan MO, Kotlyarov A, Gaestel M, Wu D, Huang CK (2004) A requirement of MAPKAPK2 in the uropod localization of PTEN during FMLP-induced neutrophil chemotaxis. Biochem Biophys Res Commun 316:666–672

    Article  CAS  PubMed  Google Scholar 

  • Xu N, Hossain M, Liu L (2013) Pharmacological inhibition of p38 mitogen-activated protein kinases affects KC/CXCL1-induced intraluminal crawling, transendothelial migration, and chemotaxis of neutrophils in vivo. Mediat Inflamm 2013:290565

    Google Scholar 

  • Xu X, Jin T (2015) The novel functions of the PLC/PKC/PKD signaling Axis in G protein-coupled receptor-mediated Chemotaxis of Neutrophils. J Immunol Res 2015:817604

    PubMed  PubMed Central  Google Scholar 

  • Xu W, Wang P, Petri B, Zhang Y, Tang W, Sun L, Kress H, Mann T, Shi Y, Kubes P, Wu D (2010) Integrin-induced PIP5K1C kinase polarization regulates neutrophil polarization, directionality, and in vivo infiltration. Immunity 33:340–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J, Wang F, Van Keymeulen A, Herzmark P, Straight A, Kelly K, Takuwa Y, Sugimoto N, Mitchison T, Bourne HR (2003) Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114:201–214

    Article  CAS  PubMed  Google Scholar 

  • Yipp BG, Petri B, Salina D, Jenne CN, Scott BN, Zbytnuik LD, Pittman K, Asaduzzaman M, Wu K, Meijndert HC, Malawista SE, de Boisfleury CA, Zhang K, Conly J, Kubes P (2012) Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med 18:1386–1393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T (1997) A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature 387:620–624

    Article  CAS  PubMed  Google Scholar 

  • Yokomizo T, Kato K, Terawaki K, Izumi T, Shimizu T (2000) A second leukotriene B(4) receptor, BLT2. A new therapeutic target in inflammation and immunological disorders. J Exp Med 192:421–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoo SK, Huttenlocher A (2011) Spatiotemporal photolabeling of neutrophil trafficking during inflammation in live zebrafish. J Leukoc Biol 89:661–667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zarbock A, Ley K (2008) Mechanisms and consequences of neutrophil interaction with the endothelium. Am J Pathol 172:1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104–107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zigmond SH (1978) Chemotaxis by polymorphonuclear leukocytes. J Cell Biol 77:269–287

    Article  CAS  PubMed  Google Scholar 

  • Zimmerman GA, McIntyre TM, Prescott SM (1997) Adhesion and signaling in vascular cell-cell interactions. J Clin Invest 100:S3–S5

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The work in the authors’ laboratories are supported by the Snyder Mouse Phenomics Resources Laboratory funded by the Snyder Institute for Chronic Diseases at the University of Calgary, Cumming School of Medicine (BP) and grant SAF2014-57845R, from the Spanish Ministry of Economy and Competiveness and the European Regional Development Fund (MJS).

Author information

Author notes

  1. Björn Petri and Maria-Jesús Sanz both contributed equally to this work.

Authors and Affiliations

  1. Snyder Institute for Chronic Diseases Mouse Phenomics Resource Laboratory, University of Calgary, Calgary, AB, T2N 4N1, Canada

    Björn Petri

  2. Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada

    Björn Petri

  3. Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain

    Maria-Jesús Sanz

  4. Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain

    Maria-Jesús Sanz

Authors
  1. Björn Petri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria-Jesús Sanz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Björn Petri or Maria-Jesús Sanz.

Ethics declarations

Conflict of interest

The authors declare that they have no financial or conflict of commercial interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Petri, B., Sanz, MJ. Neutrophil chemotaxis. Cell Tissue Res 371, 425–436 (2018). https://doi.org/10.1007/s00441-017-2776-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-017-2776-8

Keywords

Search

Navigation