Neutrophil chemotaxis

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.

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Fig. 1

References

  1. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. 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

    CAS  PubMed  Article  Google Scholar 

  3. 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

    CAS  PubMed  Article  Google Scholar 

  4. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    PubMed  PubMed Central  Article  Google Scholar 

  9. 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

    CAS  PubMed  Article  Google Scholar 

  10. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  11. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. 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

    CAS  PubMed  Article  Google Scholar 

  15. 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

    PubMed  Article  Google Scholar 

  16. 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

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  17. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 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

    PubMed  PubMed Central  Article  Google Scholar 

  19. 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

    CAS  PubMed  Article  Google Scholar 

  20. 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

    CAS  PubMed  Article  Google Scholar 

  21. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  25. 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

    CAS  PubMed  Article  Google Scholar 

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

    PubMed  Article  Google Scholar 

  27. 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

    CAS  PubMed  Article  Google Scholar 

  28. 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

    CAS  PubMed  Article  Google Scholar 

  29. 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

    CAS  PubMed  Article  Google Scholar 

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

    PubMed  PubMed Central  Article  CAS  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  32. 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

    CAS  PubMed  Article  Google Scholar 

  33. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 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

    CAS  PubMed  Article  Google Scholar 

  35. 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

    PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  42. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  44. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 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

    CAS  PubMed  Article  Google Scholar 

  46. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  48. 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

    CAS  PubMed  Article  Google Scholar 

  49. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 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

    PubMed  Article  CAS  Google Scholar 

  51. 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

    CAS  PubMed  Article  Google Scholar 

  52. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  54. 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

    CAS  PubMed  Article  Google Scholar 

  55. 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

    CAS  PubMed  Article  Google Scholar 

  56. 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

    CAS  PubMed  Article  Google Scholar 

  57. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  60. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  61. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  63. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  65. 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

    CAS  PubMed  Article  Google Scholar 

  66. 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

    CAS  PubMed  Article  Google Scholar 

  67. 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

    CAS  PubMed  Article  Google Scholar 

  68. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  71. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  75. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  78. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. 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

    CAS  PubMed  Article  Google Scholar 

  80. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  83. 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

    CAS  PubMed  Article  Google Scholar 

  84. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  87. 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

    PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    PubMed  PubMed Central  Article  Google Scholar 

  94. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  97. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  99. 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

    CAS  PubMed  Article  Google Scholar 

  100. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  101. 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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  103. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  104. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  105. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  108. 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

    CAS  PubMed  Article  Google Scholar 

  109. 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 

  110. 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 

  111. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  112. 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

    CAS  PubMed  Article  Google Scholar 

  113. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  114. 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

    CAS  PubMed  Article  Google Scholar 

  115. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  118. 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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  120. 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 

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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).

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Correspondence to Björn Petri or Maria-Jesús Sanz.

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

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Keywords

  • Neutrophils
  • Chemotaxis
  • Migration
  • Signaling
  • Chemotactic gradient