Skip to main content
SpringerLink
Log in

Cellular and molecular choreography of neutrophil recruitment to sites of sterile inflammation

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Liberation of damage-associated molecular patterns (DAMPs) following tissue injury and necrotic cell death leads to the induction of sterile inflammation. A hallmark of acute inflammation is the recruitment of neutrophils to injured tissues. This review focuses on the journey of neutrophils to sites of sterile inflammation and the cellular and molecular mechanisms that choreograph this complex voyage. We review the pathway of leukocyte recruitment, with emphasis on recent additions to our understanding of intravascular neutrophil migration. The contributions of various tissue-resident sentinel cell populations to the detection of danger signals (DAMPs) and coordination of neutrophil recruitment and migration are discussed. In addition, we highlight recent data on the control of neutrophil chemotaxis towards sites of sterile inflammation, including new insight into the temporal and spatial regulation of chemoattractant guidance signals that direct cell migration. Given that inappropriate neutrophilic inflammation is a cornerstone in the pathogenesis of many diseases, a complete understanding of the choreography of neutrophil recruitment to sites of sterile inflammation may uncover new avenues for therapeutic interventions to treat inflammatory pathologies.

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
Fig. 2

Similar content being viewed by others

References

  1. Kool M, Soullié T, van Nimwegen M, Willart MA, Muskens F, Jung S, Hoogsteden HC, Hammad H, Lambrecht BN (2008) Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med 205:869–882. doi:10.1084/jem.20071087

    Article  PubMed  CAS  Google Scholar 

  2. Yang CW, Strong BS, Miller MJ, Unanue ER (2010) Neutrophils influence the level of antigen presentation during the immune response to protein antigens in adjuvants. J Immunol 185:2927–2934. doi:10.4049/jimmunol.1001289

    Article  PubMed  CAS  Google Scholar 

  3. Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, Vermaelen K, Panaretakis T, Mignot G, Ullrich E et al (2009) Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med. doi:10.1038/nm.2028

  4. Bonasio R, Scimone ML, Schaerli P, Grabie N, Lichtman AH, von Andrian UH (2006) Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat Immunol 7:1092–1100. doi:10.1038/ni1385

    Article  PubMed  CAS  Google Scholar 

  5. Hyman MC, Petrovic-Djergovic D, Visovatti SH, Liao H, Yanamadala S, Bouïs D, Su EJ, Lawrence DA, Broekman MJ, Marcus AJ, Pinsky DJ (2009) Self-regulation of inflammatory cell trafficking in mice by the leukocyte surface apyrase CD39. J Clin Invest. doi:10.1172/JCI36433

  6. Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204:3037–3047. doi:10.1084/jem.20070885

    Article  PubMed  CAS  Google Scholar 

  7. Tsung A, Sahai R, Tanaka H, Nakao A, Fink MP, Lotze M, Yang H, Li J, Tracey K, Geller DA, Billiar TR (2005) The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J Exp Med 201:1135–1143. doi:10.1084/jem.20042614

    Article  PubMed  CAS  Google Scholar 

  8. Krüger B, Krick S, Dhillon N, Lerner SM, Ames S, Bromberg JS, Lin M, Walsh L, Vella J, Fischereder M et al (2009) Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proc Natl Acad Sci USA 106:3390–3395. doi:10.1073/pnas.0810169106

    Article  PubMed  Google Scholar 

  9. Shi Y, Evans JE, Rock K (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–521. doi:10.1038/nature01991

    Article  PubMed  CAS  Google Scholar 

  10. Shi Y, Galusha SA, Rock K (2006) Cutting edge: elimination of an endogenous adjuvant reduces the activation of CD8 T lymphocytes to transplanted cells and in an autoimmune diabetes model. J Immunol 176:3905–3908

    PubMed  CAS  Google Scholar 

  11. 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. doi:10.1038/nature08780

    Article  PubMed  CAS  Google Scholar 

  12. Imaeda AB, Watanabe A, Sohail MA, Mahmood S, Mohamadnejad M, Sutterwala FS, Flavell RA, Mehal WZ (2009) Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J Clin Invest 119:305–314. doi:10.1172/JCI35958

    PubMed  CAS  Google Scholar 

  13. Kono H, Rock K (2008) How dying cells alert the immune system to danger. Nat Rev Immunol 8:279–289. doi:10.1038/nri2215

    Article  PubMed  CAS  Google Scholar 

  14. Chen CJ, Kono H, Golenbock D, Reed G, Akira S, Rock K (2007) Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med 13:851–856. doi:10.1038/nm1603

    Article  PubMed  CAS  Google Scholar 

  15. Butcher EC (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67:1033–1036

    Article  PubMed  CAS  Google Scholar 

  16. Ley K, Gaehtgens P, Fennie C, Singer MS, Lasky LA, Rosen SD (1991) Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo. Blood 77:2553–2555

    PubMed  CAS  Google Scholar 

  17. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314

    Article  PubMed  CAS  Google Scholar 

  18. von Andrian UH, Chambers JD, McEvoy LM, Bargatze RF, Arfors KE, Butcher EC (1991) Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. Proc Natl Acad Sci USA 88:7538–7542

    Article  Google Scholar 

  19. Borregaard N (2010) Neutrophils, from marrow to microbes. Immunity 33:657–670. doi:10.1016/j.immuni.2010.11.011

    Article  PubMed  CAS  Google Scholar 

  20. Ley K, Laudanna C, Cybulsky M, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689. doi:10.1038/nri2156

    Article  PubMed  CAS  Google Scholar 

  21. Luo BH, Carman CV, Springer TA (2007) Structural basis of integrin regulation and signaling. Annu Rev Immunol 25:619–647. doi:10.1146/annurev.immunol.25.022106.141618

    Article  PubMed  CAS  Google Scholar 

  22. Giagulli C, Ottoboni L, Caveggion E, Rossi B, Lowell C, Constantin G, Laudanna C, Berton G (2006) The Src family kinases Hck and Fgr are dispensable for inside-out, chemoattractant-induced signaling regulating beta 2 integrin affinity and valency in neutrophils, but are required for beta 2 integrin-mediated outside-in signaling involved in sustained adhesion. J Immunol 177:604–611

    PubMed  CAS  Google Scholar 

  23. McDonald B, McAvoy EF, Lam F, Gill V, de la Motte C, Savani RC, Kubes P (2008) Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med 205:915–927. doi:10.1084/jem.20071765

    Article  PubMed  CAS  Google Scholar 

  24. Mizgerd JP, Kubo H, Kutkoski GJ, Bhagwan SD, Scharffetter-Kochanek K, Beaudet AL, Doerschuk CM (1997) Neutrophil emigration in the skin, lungs, and peritoneum: different requirements for CD11/CD18 revealed by CD18-deficient mice. J Exp Med 186:1357–1364

    Article  PubMed  CAS  Google Scholar 

  25. Wong J, Johnston B, Lee SS, Bullard DC, Smith CW, Beaudet AL, Kubes P (1997) A minimal role for selectins in the recruitment of leukocytes into the inflamed liver microvasculature. J Clin Invest 99:2782–2790. doi:10.1172/JCI119468

    Article  PubMed  CAS  Google Scholar 

  26. Kuligowski MP, Kitching AR, Hickey M (2006) Leukocyte recruitment to the inflamed glomerulus: a critical role for platelet-derived P-selectin in the absence of rolling. J Immunol 176:6991–6999

    PubMed  CAS  Google Scholar 

  27. 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. doi:10.1084/jem.20060925

    Article  PubMed  CAS  Google Scholar 

  28. Massena S, Christoffersson G, Hjertström 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. doi:10.1182/blood-2010-01-266072

  29. Carman CV, Springer TA (2008) Trans-cellular migration: cell-cell contacts get intimate. Curr Opin Cell Biol 20:533–540. doi:10.1016/j.ceb.2008.05.007

    Article  PubMed  CAS  Google Scholar 

  30. Feng D, Nagy JA, Pyne K, Dvorak HF, Dvorak AM (1998) Neutrophils emigrate from venules by a transendothelial cell pathway in response to FMLP. J Exp Med 187:903–915

    Article  PubMed  CAS  Google Scholar 

  31. Woodfin A, Voisin MB, Nourshargh S (2010) Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol 17:9–17. doi:10.1097/MOH.0b013e3283333930

    Article  PubMed  Google Scholar 

  32. Wong CH, Heit B, Kubes P (2010) Molecular regulators of leucocyte chemotaxis during inflammation. Cardiovasc Res 86:183–191. doi:10.1093/cvr/cvq040

    Article  PubMed  CAS  Google Scholar 

  33. Chen GY, Nuñez G (2010) Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol 10:826–837. doi:10.1038/nri2873

    Article  PubMed  CAS  Google Scholar 

  34. Rock K, Latz E, Ontiveros F, Kono H (2010) The sterile inflammatory response. Annu Rev Immunol 28:321–342. doi:10.1146/annurev-immunol-030409-101311

    Article  PubMed  CAS  Google Scholar 

  35. Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, Prestwich GD, Mascarenhas MM, Garg HG, Quinn DA et al (2005) Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med 11:1173–1179. doi:10.1038/nm1315

    Article  PubMed  CAS  Google Scholar 

  36. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA et al (2009) CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. doi:10.1038/ni.1836

  37. Tsung A, Klune JR, Zhang X, Jeyabalan G, Cao Z, Peng X, Stolz DB, Geller DA, Rosengart MR, Billiar TR (2007) HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. J Exp Med 204:2913–2923. doi:10.1084/jem.20070247

    Article  PubMed  CAS  Google Scholar 

  38. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M et al (2010) NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357–1361. doi:10.1038/nature08938

    Article  PubMed  CAS  Google Scholar 

  39. Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, Ulland TK, Eisenbarth SC, Florquin S, Flavell RA, Leemans JC, Sutterwala FS (2009) Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci USA 106:20388–20393. doi:10.1073/pnas.0908698106

    Article  PubMed  CAS  Google Scholar 

  40. Li H, Ambade A, Re F (2009) Cutting edge: necrosis activates the NLRP3 inflammasome. J Immunol 183:1528–1532. doi:10.4049/jimmunol.0901080

    Article  PubMed  CAS  Google Scholar 

  41. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241. doi:10.1038/nature04516

    Article  PubMed  CAS  Google Scholar 

  42. Muruve DA, Pétrilli V, Zaiss AK, White LR, Clark SA, Ross PJ, Parks RJ, Tschopp J (2008) The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452:103–107. doi:10.1038/nature06664

    Article  PubMed  CAS  Google Scholar 

  43. Basu S, Binder RJ, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14:303–313

    Article  PubMed  CAS  Google Scholar 

  44. Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P et al (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97:889–901

    Article  PubMed  CAS  Google Scholar 

  45. Taylor KR, Yamasaki K, Radek KA, Di Nardo A, Goodarzi H, Golenbock D, Beutler B, Gallo RL (2007) Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependent on Toll-like receptor 4, CD44, and MD-2. J Biol Chem 282:18265–18275. doi:10.1074/jbc.M606352200

    Article  PubMed  CAS  Google Scholar 

  46. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195. doi:10.1038/nature00858

    Article  PubMed  CAS  Google Scholar 

  47. 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. doi:10.1126/science.1195491

    Article  PubMed  CAS  Google Scholar 

  48. Kono H, Karmarkar D, Iwakura Y, Rock K (2010) Identification of the cellular sensor that stimulates the inflammatory response to sterile cell death. J Immunol 184:4470–4478. doi:10.4049/jimmunol.0902485

    Article  PubMed  CAS  Google Scholar 

  49. Soehnlein O, Lindbom L (2010) Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol 10:427–439. doi:10.1038/nri2779

    Article  PubMed  CAS  Google Scholar 

  50. Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, Sarnacki S, Cumano A, Lauvau G, Geissmann F (2007) Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317:666–670. doi:10.1126/science.1142883

    Article  PubMed  CAS  Google Scholar 

  51. Harja E, Bu DX, Hudson BI, Chang JS, Shen X, Hallam K, Kalea AZ, Lu Y, Rosario RH, Oruganti S et al (2008) Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE−/− mice. J Clin Invest 118:183–194. doi:10.1172/JCI32703

    Article  PubMed  CAS  Google Scholar 

  52. Opitz B, Hippenstiel S, Eitel J, Suttorp N (2007) Extra- and intracellular innate immune recognition in endothelial cells. Thromb Haemost 98:319–326

    PubMed  CAS  Google Scholar 

  53. Taylor KR, Trowbridge JM, Rudisill JA, Termeer CC, Simon JC, Gallo RL (2004) Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem 279:17079–17084. doi:10.1074/jbc.M310859200

    Article  PubMed  CAS  Google Scholar 

  54. Andonegui G, Bonder CS, Green F, Mullaly SC, Zbytnuik L, Raharjo E, Kubes P (2003) Endothelium-derived Toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs. J Clin Invest 111:1011–1020. doi:10.1172/JCI16510

    PubMed  CAS  Google Scholar 

  55. Andonegui G, Zhou H, Bullard D, Kelly MM, Mullaly SC, McDonald B, Long EM, Robbins SM, Kubes P (2009) Mice that exclusively express TLR4 on endothelial cells can efficiently clear a lethal systemic Gram-negative bacterial infection. J Clin Invest 119:1921–1930

    PubMed  CAS  Google Scholar 

  56. Ye X, Ding J, Zhou X, Chen G, Liu SF (2008) Divergent roles of endothelial NF-kappaB in multiple organ injury and bacterial clearance in mouse models of sepsis. J Exp Med 205:1303–1315. doi:10.1084/jem.20071393

    Article  PubMed  CAS  Google Scholar 

  57. Vilaysane A, Chun J, Seamone ME, Wang W, Chin R, Hirota S, Li Y, Clark SA, Tschopp J, Trpkov K, Hemmelgarn BR et al (2010) The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J Am Soc Nephrol 21:1732–1744. doi:10.1681/ASN.2010020143

    Article  PubMed  CAS  Google Scholar 

  58. Eigenbrod T, Park JH, Harder J, Iwakura Y, Núñez G (2008) Cutting edge: critical role for mesothelial cells in necrosis-induced inflammation through the recognition of IL-1 alpha released from dying cells. J Immunol 181:8194–8198

    PubMed  CAS  Google Scholar 

  59. Bonneville M, O'Brien RL, Born WK (2010) Gammadelta T cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol 10:467–478. doi:10.1038/nri2781

    Article  PubMed  CAS  Google Scholar 

  60. Askenase PW, Itakura A, Leite-de-Moraes MC, Lisbonne M, Roongapinun S, Goldstein DR, Szczepanik M (2005) TLR-dependent IL-4 production by invariant Valpha14+Jalpha18+ NKT cells to initiate contact sensitivity in vivo. J Immunol 175:6390–6401

    PubMed  CAS  Google Scholar 

  61. Gapin L (2010) iNKT cell autoreactivity: what is 'self' and how is it recognized? Nat Rev Immunol 10:272–277. doi:10.1038/nri2743

    Article  PubMed  CAS  Google Scholar 

  62. Liu Y, Teige A, Mondoc E, Ibrahim S, Holmdahl R, Issazadeh-Navikas S (2011) Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice. J Clin Invest 121:249–264. doi:10.1172/JCI43964

    Article  PubMed  CAS  Google Scholar 

  63. Semple JW, Italiano JE, Freedman J (2011) Platelets and the immune continuum. Nat Rev Immunol 11:264–274. doi:10.1038/nri2956

    Article  PubMed  CAS  Google Scholar 

  64. Lindemann S, Tolley ND, Dixon DA, McIntyre TM, Prescott SM, Zimmerman GA, Weyrich AS (2001) Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 154:485–490. doi:10.1083/jcb.200105058

    Article  PubMed  CAS  Google Scholar 

  65. Boilard E, Nigrovic PA, Larabee K, Watts GF, Coblyn JS, Weinblatt ME, Massarotti EM, Remold-O'Donnell E, Farndale RW, Ware J, Lee DM (2010) Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 327:580–583. doi:10.1126/science.1181928

    Article  PubMed  CAS  Google Scholar 

  66. Huo Y, Schober A, Forlow SB, Smith DF, Hyman MC, Jung S, Littman DR, Weber C, Ley K (2003) Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 9:61–67. doi:10.1038/nm810

    Article  PubMed  CAS  Google Scholar 

  67. Ley K (2002) Integration of inflammatory signals by rolling neutrophils. Immunol Rev 186:8–18

    Article  PubMed  CAS  Google Scholar 

  68. Luster AD, Alon R, von Andrian UH (2005) Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol 6:1182–1190. doi:10.1038/ni1275

    Article  PubMed  CAS  Google Scholar 

  69. 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. doi:10.1016/j.immuni.2010.07.018

    Article  PubMed  CAS  Google Scholar 

  70. Ramos CD, Canetti C, Souto JT, Silva JS, Hogaboam CM, Ferreira SH, Cunha FQ (2005) MIP-1alpha[CCL3] acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential release of TNF-alpha and LTB4. J Leukoc Biol 78:167–177. doi:10.1189/jlb.0404237

    Article  PubMed  CAS  Google Scholar 

  71. Viola A, Luster AD (2008) Chemokines and their receptors: drug targets in immunity and inflammation. Annu Rev Pharmacol Toxicol 48:171–197. doi:10.1146/annurev.pharmtox.48.121806.154841

    Article  PubMed  CAS  Google Scholar 

  72. Liu Y, Mei J, Gonzales L, Yang G, Dai N, Wang P, Zhang P, Favara M, Malcolm KC, Guttentag S, Worthen GS (2011) IL-17A and TNF-alpha exert synergistic effects on expression of CXCL5 by alveolar type II cells in vivo and in vitro. J Immunol 186:3197–3205. doi:10.4049/jimmunol.1002016

    Article  PubMed  CAS  Google Scholar 

  73. 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. doi:10.1038/nm1361

    Article  PubMed  CAS  Google Scholar 

  74. Snelgrove RJ, Jackson PL, Hardison MT, Noerager BD, Kinloch A, Gaggar A, Shastry S, Rowe SM, Shim YM, Hussell T, Blalock JE (2010) A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation. Science 330:90–94. doi:10.1126/science.1190594

    Article  PubMed  CAS  Google Scholar 

  75. Carp H (1982) Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils. J Exp Med 155:264–275

    Article  PubMed  CAS  Google Scholar 

  76. Galper JB (1974) Mitochondrial protein synthesis in HeLa cells. J Cell Biol 60:755–763

    Article  PubMed  CAS  Google Scholar 

  77. Foxman EF, Campbell JJ, Butcher EC (1997) Multistep navigation and the combinatorial control of leukocyte chemotaxis. J Cell Biol 139:1349–1360

    Article  PubMed  CAS  Google Scholar 

  78. 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. doi:10.1038/ni.1623

    Article  PubMed  CAS  Google Scholar 

  79. 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. doi:10.1083/jcb.200202114

    Article  PubMed  CAS  Google Scholar 

  80. 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 USA 106:4018–4023. doi:10.1073/pnas.0900196106

    Article  PubMed  CAS  Google Scholar 

  81. Khan AI, Heit B, Andonegui G, Colarusso P, Kubes P (2005) Lipopolysaccharide: a p38 MAPK-dependent disrupter of neutrophil chemotaxis. Microcirculation 12:421–432. doi:10.1080/10739680590960368

    Article  PubMed  CAS  Google Scholar 

  82. Ariel A, Fredman G, Sun YP, Kantarci A, Van Dyke TE, Luster AD, Serhan CN (2006) Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nat Immunol 7:1209–1216. doi:10.1038/ni1392

    Article  PubMed  CAS  Google Scholar 

  83. Serhan CN, Yacoubian S, Yang R (2008) Anti-inflammatory and proresolving lipid mediators. Ann Rev Pathol 3:279–312. doi:10.1146/annurev.pathmechdis.3.121806.151409

    Article  CAS  Google Scholar 

  84. Soehnlein O, Zernecke A, Eriksson EE, Rothfuchs AG, Pham CT, Herwald H, Bidzhekov K, Rottenberg ME, Weber C, Lindbom L (2008) Neutrophil secretion products pave the way for inflammatory monocytes. Blood 112:1461–1471. doi:10.1182/blood-2008-02-139634

    Article  PubMed  CAS  Google Scholar 

  85. Chen GY, Tang J, Zheng P, Liu Y (2009) CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323:1722–1725. doi:10.1126/science.1168988

    Article  PubMed  CAS  Google Scholar 

  86. 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. doi:10.1172/JCI5208

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Work in the authors’ laboratory is supported by Canadian Institutes for Health Research operating grants and group grant, as well as the Canadian Foundation for Innovation. B.M. is supported by an MD/PhD studentship from the Alberta Heritage Foundation for Medical Research (Alberta Innovates Health Solutions). P.K. is an Alberta Heritage Foundation for Medical Research (AIHS) Scientist and the Snyder Chair in Critical Care Medicine.

Conflict of interests

The authors declare no competing financial interests.

Author information

Authors and Affiliations

  1. Snyder Institute of Infection, Immunity, and Inflammation, University of Calgary, Alberta, Canada

    Braedon McDonald & Paul Kubes

  2. Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada

    Paul Kubes

Authors
  1. Braedon McDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Kubes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul Kubes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McDonald, B., Kubes, P. Cellular and molecular choreography of neutrophil recruitment to sites of sterile inflammation. J Mol Med 89, 1079–1088 (2011). https://doi.org/10.1007/s00109-011-0784-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-011-0784-9

Keywords

Search

Navigation