Skip to main content

Advertisement

SpringerLink
Log in

Pleiotropic regulations of neutrophil receptors response to sepsis

  • Review
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Introduction

Sepsis is a complex clinical condition that causes a high mortality rate worldwide. Numerous studies on the pathophysiology of sepsis have revealed an imbalance in the inflammatory network, thus leading to tissue damage, organ failure, and ultimately death. The impairment of neu­trophil migration is associated with the outcome of sepsis.

Methods

Literature review was performed on the roles of neutrophil recruitment and neutrophil receptors as pleiotropic regulators during sepsis. Additionally, we systematically classify neutrophil receptors with regard to the neutrophil response during sepsis and discuss the clinical implications of these receptors for the treatment of sepsis.

Results

Increasing evidence suggests that there is significant dysfunction in neutrophil recruitment during sepsis, characterized by the failure to migrate to the site of infection. Neutrophil receptors, as pleiotropic regulators, play important roles in the neutrophil response during sepsis.

Conclusions

Neutrophil receptors play key roles in chemotactic neutrophil migration and may prove to be suitable targets in future pharmacological therapies for sepsis.

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

Abbreviations

BLTs:

Leukotriene B4 receptors

C5aR:

Complement factor 5a receptors

CCRs:

CC chemokine receptors

CLP:

Cecal ligation and puncture

CpG:

Cytosine-phosphate-guanine

CXCRs:

C-X-C chemokine receptors

ERK1/2:

Extracellular signal-regulated kinase 1/2

FcR:

Fc-receptors

fMLP:

Formyl-methionyl-leucyl-phenylalanine

FPRs:

Formyl-peptide receptors

GRK:

G-protein-coupled receptor kinase

IL-1:

Interleukin-1

IL-10/IL-10R:

Interleukin-10/interleukin-10 receptor

IL-33:

Interleukin-33

IL-8:

Interleukin-8

iNOS:

Inducible NO synthase

IRAKs:

IL-1R-associated kinases

LOX-1:

Lectin-like oxidized low-density lipoprotein receptor-1

LPS:

Lipopolysaccharide

LTA:

Lipoteichoic acid

MAPK:

Mitogen-activated protein kinase

MIP-2:

Macrophage inflammatory protein-2

MyD88:

Myeloid differentiation factor-88

NF-κB:

Nuclear factor-κB

NO:

Nitric oxide

ODN:

Oligonucleotides

PAFRs:

Plate-activating factor receptors

PI3 Kγ:

Phosphatidylinositol-3-kinase γ

PMNs:

Polymorphonuclear leukocytes

PPARs:

Peroxisome proliferator-activated

PPARγ:

Peroxisome proliferator-activated receptor-γreceptor

sGC:

Soluble guanylate cyclase

SL-CLP:

Sublethal CLP

ST2R:

IL-33 receptor ST2

STAT3:

Signal transducer and activator of transcription 3

STAT6:

Signal transducerand activator of transcription 6

TLRs:

Toll like receptors

TNFR:

Tumor necrosis factor receptor

TNF-α:

Tumor necrosis factor-α

References

  1. Chang HJ, Lynm C, Glass RM. JAMA patient page. Sepsis. JAMA. 2010;304(16):1856. doi:10.1001/jama.304.16.1856.

    Article  CAS  PubMed  Google Scholar 

  2. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369(9):840–51. doi:10.1056/NEJMra1208623.

    Article  CAS  PubMed  Google Scholar 

  3. Jenne CN, Wong CH, Zemp FJ, McDonald B, Rahman MM, Forsyth PA, McFadden G, Kubes P. Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps. Cell Host Microbe. 2013;13(2):169–80. doi:10.1016/j.chom.2013.01.005.

    Article  CAS  PubMed  Google Scholar 

  4. Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu Rev Immunol. 2012;30:459–89. doi:10.1146/annurev-immunol-020711-074942.

    Article  CAS  PubMed  Google Scholar 

  5. Alves-Filho JC, Benjamim C, Tavares-Murta BM, Cunha FQ. Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome. Mem Inst Oswaldo Cruz. 2005;100(Suppl 1):223–6. doi:10.1590/S0074-02762005000900038.

    Article  CAS  PubMed  Google Scholar 

  6. Silva MT. Macrophage phagocytosis of neutrophils at inflammatory/infectious foci: a cooperative mechanism in the control of infection and infectious inflammation. J Leukoc Biol. 2011;89(5):675–83. doi:10.1189/jlb.0910536.

    Article  CAS  PubMed  Google Scholar 

  7. Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011;11(8):519–31. doi:10.1038/nri3024.

    Article  CAS  PubMed  Google Scholar 

  8. Bradley LM, Douglass MF, Chatterjee D, Akira S, Baaten BJ. Matrix metalloprotease 9 mediates neutrophil migration into the airways in response to influenza virus-induced toll-like receptor signaling. PLoS Pathog. 2012;8(4):e1002641. doi:10.1371/journal.ppat.1002641.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13(3):159–75. doi:10.1038/nri3399.

    Article  CAS  PubMed  Google Scholar 

  10. Alves-Filho JC, de Freitas A, Spiller F, Souto FO, Cunha FQ. The role of neutrophils in severe sepsis. Shock. 2008;30(Suppl 1):3–9. doi:10.1097/SHK.0b013e3181818466.

    Article  CAS  PubMed  Google Scholar 

  11. Reddy RC, Standiford TJ. Effects of sepsis on neutrophil chemotaxis. Curr Opin Hematol. 2010;17(1):18–24. doi:10.1097/MOH.0b013e32833338f3.

    Article  CAS  PubMed  Google Scholar 

  12. Alves-Filho JC, de Freitas A, Russo M, Cunha FQ. Toll-like receptor 4 signaling leads to neutrophil migration impairment in polymicrobial sepsis. Crit Care Med. 2006;34(2):461–70.

    Article  CAS  PubMed  Google Scholar 

  13. Sun L, Ye RD. Role of G protein-coupled receptors in inflammation. Acta Pharmacol Sin. 2012;33(3):342–50. doi:10.1038/aps.2011.200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Migeotte I, Communi D, Parmentier M. Formyl peptide receptors: a promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev. 2006;17(6):501–19. doi:10.1016/j.cytogfr.2006.09.009.

    Article  CAS  PubMed  Google Scholar 

  15. Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM. Platelet-activating factor, a pleiotrophic mediator of physiological and pathological processes. Crit Rev Clin Lab Sci. 2003;40(6):643–72. doi:10.1080/714037693.

    Article  CAS  PubMed  Google Scholar 

  16. Lee H, Whitfeld PL, Mackay CR. Receptors for complement C5a. The importance of C5aR and the enigmatic role of C5L2. Immunol Cell Biol. 2008;86(2):153–60. doi:10.1038/sj.icb.7100166.

    Article  CAS  PubMed  Google Scholar 

  17. Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, Power CA. International union of pharmacology XXII. Nomenclature for chemokine receptors. Pharmacol Rev. 2000;52(1):145–76.

    CAS  PubMed  Google Scholar 

  18. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006;354(6):610–21. doi:10.1056/NEJMra052723.

    Article  CAS  PubMed  Google Scholar 

  19. Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, Dewor M, Georgiev I, Schober A, Leng L, Kooistra T, Fingerle-Rowson G, Ghezzi P, Kleemann R, McColl SR, Bucala R, Hickey MJ, Weber C. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med. 2007;13(5):587–96. doi:10.1038/nm1567.

    Article  CAS  PubMed  Google Scholar 

  20. Barlic J, Andrews JD, Kelvin AA, Bosinger SE, DeVries ME, Xu L, Dobransky T, Feldman RD, Ferguson SS, Kelvin DJ. Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI. Nat Immunol. 2000;1(3):227–33. doi:10.1038/79767.

    Article  CAS  PubMed  Google Scholar 

  21. Cummings CJ, Martin TR, Frevert CW, Quan JM, Wong VA, Mongovin SM, Hagen TR, Steinberg KP, Goodman RB. Expression and function of the chemokine receptors CXCR1 and CXCR2 in sepsis. J Immunol. 1999;162(4):2341–6.

    CAS  PubMed  Google Scholar 

  22. Arraes SM, Freitas MS, da Silva SV, de Paula Neto HA, Alves-Filho JC, Auxiliadora Martins M, Basile-Filho A, Tavares-Murta BM, Barja-Fidalgo C, Cunha FQ. Impaired neutrophil chemotaxis in sepsis associates with GRK expression and inhibition of actin assembly and tyrosine phosphorylation. Blood. 2006;108(9):2906–13. doi:10.1182/blood-2006-05-024638.

    Article  CAS  PubMed  Google Scholar 

  23. Chishti AD, Shenton BK, Kirby JA, Baudouin SV. Neutrophil chemotaxis and receptor expression in clinical septic shock. Intensive Care Med. 2004;30(4):605–11. doi:10.1007/s00134-004-2175-y.

    Article  PubMed  Google Scholar 

  24. Rios-Santos F, Alves-Filho JC, Souto FO, Spiller F, Freitas A, Lotufo CM, Soares MB, Dos Santos RR, Teixeira MM, Cunha FQ. Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide. Am J Respir Crit Care Med. 2007;175(5):490–7. doi:10.1164/rccm.200601-103OC.

    Article  CAS  PubMed  Google Scholar 

  25. Alves-Filho JC, Freitas A, Souto FO, Spiller F, Paula-Neto H, Silva JS, Gazzinelli RT, Teixeira MM, Ferreira SH, Cunha FQ. Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis. Proc Natl Acad Sci USA. 2009;106(10):4018–23. doi:10.1073/pnas.0900196106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Trevelin SC, Alves-Filho JC, Sonego F, Turato W, Nascimento DC, Souto FO, Cunha TM, Gazzinelli RT, Cunha FQ. Toll-like receptor 9 activation in neutrophils impairs chemotaxis and reduces sepsis outcome. Crit Care Med. 2012;40(9):2631–7. doi:10.1097/CCM.0b013e318258fb70.

    Article  CAS  PubMed  Google Scholar 

  27. Evron T, Daigle TL, Caron MG. GRK2: multiple roles beyond G protein-coupled receptor desensitization. Trends Pharmacol Sci. 2012;33(3):154–64. doi:10.1016/j.tips.2011.12.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dal Secco D, Moreira AP, Freitas A, Silva JS, Rossi MA, Ferreira SH, Cunha FQ. Nitric oxide inhibits neutrophil migration by a mechanism dependent on ICAM-1: role of soluble guanylate cyclase. Nitric Oxide. 2006;15(1):77–86. doi:10.1016/j.niox.2006.02.004.

    Article  CAS  PubMed  Google Scholar 

  29. Zhao Y, Brandish PE, Di Valentin M, Schelvis JP, Babcock GT, Marletta MA. Inhibition of soluble guanylate cyclase by ODQ. Biochemistry. 2000;39(35):10848–54.

    Article  CAS  PubMed  Google Scholar 

  30. Martin EL, Souza DG, Fagundes CT, Amaral FA, Assenzio B, Puntorieri V, Del Sorbo L, Fanelli V, Bosco M, Delsedime L, Pinho JF, Lemos VS, Souto FO, Alves-Filho JC, Cunha FQ, Slutsky AS, Ruckle T, Hirsch E, Teixeira MM, Ranieri VM. Phosphoinositide-3 kinase gamma activity contributes to sepsis and organ damage by altering neutrophil recruitment. Am J Respir Crit Care Med. 2010;182(6):762–73. doi:10.1164/rccm.201001-0088OC.

    Article  CAS  PubMed  Google Scholar 

  31. Sonego F, Alves-Filho JC, Cunha FQ. Targeting neutrophils in sepsis. Expert Rev Clin Immunol. 2014;10(8):1019–28. doi:10.1586/1744666X.2014.922876.

    Article  CAS  PubMed  Google Scholar 

  32. Mishra HK, Johnson TJ, Seelig DM, Walcheck B. Targeting ADAM17 in leukocytes increases neutrophil recruitment and reduces bacterial spread during polymicrobial sepsis. J Leukoc Biol. 2016;. doi:10.1189/jlb.3VMAB1115-496RR.

    PubMed  Google Scholar 

  33. Guerrero AT, Zarpelon AC, Vieira SM, Pinto LG, Ferreira SH, Cunha FQ, Verri WA Jr, Cunha TM. The role of PAF/PAFR signaling in zymosan-induced articular inflammatory hyperalgesia. Naunyn Schmiedebergs Arch Pharmacol. 2013;386(1):51–9. doi:10.1007/s00210-012-0813-4.

    Article  CAS  PubMed  Google Scholar 

  34. Roth M, Nauck M, Yousefi S, Tamm M, Blaser K, Perruchoud AP, Simon HU. Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor. J Exp Med. 1996;184(1):191–201.

    Article  CAS  PubMed  Google Scholar 

  35. Dyer KD, Percopo CM, Xie Z, Yang Z, Kim JD, Davoine F, Lacy P, Druey KM, Moqbel R, Rosenberg HF. Mouse and human eosinophils degranulate in response to platelet-activating factor (PAF) and lysoPAF via a PAF-receptor-independent mechanism: evidence for a novel receptor. J Immunol. 2010;184(11):6327–34. doi:10.4049/jimmunol.0904043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Moreno SE, Alves-Filho JC, Rios-Santos F, Silva JS, Ferreira SH, Cunha FQ, Teixeira MM. Signaling via platelet-activating factor receptors accounts for the impairment of neutrophil migration in polymicrobial sepsis. J Immunol. 2006;177(2):1264–71.

    Article  CAS  PubMed  Google Scholar 

  37. McCullers JA, Rehg JE. Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor. J Infect Dis. 2002;186(3):341–50. doi:10.1086/341462.

    Article  CAS  PubMed  Google Scholar 

  38. Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang M, Mackay CR, Zetoune FS, Gerard NP, Cianflone K, Kohl J, Gerard C, Sarma JV, Ward PA. Functional roles for C5a receptors in sepsis. Nat Med. 2008;14(5):551–7. doi:10.1038/nm1753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ward PA. The dark side of C5a in sepsis. Nat Rev Immunol. 2004;4(2):133–42. doi:10.1038/nri1269.

    Article  CAS  PubMed  Google Scholar 

  40. Guo RF, Riedemann NC, Bernacki KD, Sarma VJ, Laudes IJ, Reuben JS, Younkin EM, Neff TA, Paulauskis JD, Zetoune FS, Ward PA. Neutrophil C5a receptor and the outcome in a rat model of sepsis. FASEB J. 2003;17(13):1889–91. doi:10.1096/fj.03-0009fje.

    CAS  PubMed  Google Scholar 

  41. Seely AJ, Naud JF, Campisi G, Giannias B, Liu S, DiCarlo A, Ferri LE, Pascual JL, Tchervenkov J, Christou NV. Alteration of chemoattractant receptor expression regulates human neutrophil chemotaxis in vivo. Ann Surg. 2002;235(4):550–9.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Bamberg CE, Mackay CR, Lee H, Zahra D, Jackson J, Lim YS, Whitfeld PL, Craig S, Corsini E, Lu B, Gerard C, Gerard NP. The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction. J Biol Chem. 2010;285(10):7633–44. doi:10.1074/jbc.M109.092106.

    Article  CAS  PubMed  Google Scholar 

  43. Ward PA. Role of the complement in experimental sepsis. J Leukoc Biol. 2008;83(3):467–70. doi:10.1189/jlb.0607376.

    Article  CAS  PubMed  Google Scholar 

  44. Ward PA. The harmful role of c5a on innate immunity in sepsis. J Innate Immun. 2010;2(5):439–45. doi:10.1159/000317194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Le Y, Murphy PM, Wang JM. Formyl-peptide receptors revisited. Trends Immunol. 2002;23(11):541–8.

    Article  CAS  PubMed  Google Scholar 

  46. Sun R, Iribarren P, Zhang N, Zhou Y, Gong W, Cho EH, Lockett S, Chertov O, Bednar F, Rogers TJ, Oppenheim JJ, Wang JM. Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor. J Immunol. 2004;173(1):428–36.

    Article  CAS  PubMed  Google Scholar 

  47. Cavicchioni G, Fraulini A, Turchetti M, Varani K, Falzarano S, Pavan B, Spisani S. Biological activity of for-Met-Leu-Phe-OMe analogs: relevant substitutions specifically trigger killing mechanisms in human neutrophils. Eur J Pharmacol. 2005;512(1):1–8. doi:10.1016/j.ejphar.2005.02.013.

    Article  CAS  PubMed  Google Scholar 

  48. Rabiet MJ, Huet E, Boulay F. Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR. Eur J Immunol. 2005;35(8):2486–95. doi:10.1002/eji.200526338.

    Article  CAS  PubMed  Google Scholar 

  49. Liu M, Zhao J, Chen K, Bian X, Wang C, Shi Y, Wang JM. G protein-coupled receptor FPR1 as a pharmacologic target in inflammation and human glioblastoma. Int Immunopharmacol. 2012;14(3):283–8. doi:10.1016/j.intimp.2012.07.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Liu X, Ma B, Malik AB, Tang H, Yang T, Sun B, Wang G, Minshall RD, Li Y, Zhao Y, Ye RD, Xu J. Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases. Nat Immunol. 2012;13(5):457–64. doi:10.1038/ni.2258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Heit B, Liu L, Colarusso P, Puri KD, Kubes P. PI3 K accelerates, but is not required for, neutrophil chemotaxis to fMLP. J Cell Sci. 2008;121(Pt 2):205–14. doi:10.1242/jcs.020412.

    Article  CAS  PubMed  Google Scholar 

  52. Kinzer-Ursem TL, Sutton KL, Waller A, Omann GM, Linderman JJ. Multiple receptor states are required to describe both kinetic binding and activation of neutrophils via N-formyl peptide receptor ligands. Cell Signal. 2006;18(10):1732–47. doi:10.1016/j.cellsig.2006.01.014.

    Article  CAS  PubMed  Google Scholar 

  53. Waller A, Sutton KL, Kinzer-Ursem TL, Absood A, Traynor JR, Linderman JJ, Omann GM. Receptor binding kinetics and cellular responses of six N-formyl peptide agonists in human neutrophils. Biochemistry. 2004;43(25):8204–16. doi:10.1021/bi035335i.

    Article  CAS  PubMed  Google Scholar 

  54. Herrmann JM, Bernardo J, Long HJ, Seetoo K, McMenamin ME, Batista EL Jr, Van Dyke TE, Simons ER. Sequential chemotactic and phagocytic activation of human polymorphonuclear neutrophils. Infect Immun. 2007;75(8):3989–98. doi:10.1128/IAI.00388-07.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Oyoshi MK, He R, Li Y, Mondal S, Yoon J, Afshar R, Chen M, Lee DM, Luo HR, Luster AD, Cho JS, Miller LS, Larson A, Murphy GF, Geha RS. Leukotriene B4-driven neutrophil recruitment to the skin is essential for allergic skin inflammation. Immunity. 2012;37(4):747–58. doi:10.1016/j.immuni.2012.06.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Monteiro AP, Soledade E, Pinheiro CS, Dellatorre-Teixeira L, Oliveira GP, Oliveira MG, Peters-Golden M, Rocco PR, Benjamim CF, Canetti C. Pivotal role of the 5-lipoxygenase pathway in lung injury after experimental sepsis. Am J Respir Cell Mol Biol. 2014;50(1):87–95. doi:10.1165/rcmb.2012-0525OC.

    CAS  PubMed  Google Scholar 

  57. Li XJ, Fu HY, Yi WJ, Zhao YJ, Wang J, Li JB, Wang JF, Deng XM. Dual role of leukotriene B4 receptor type 1 in experimental sepsis. J Surg Res. 2015;193(2):902–8. doi:10.1016/j.jss.2014.09.013.

    Article  CAS  PubMed  Google Scholar 

  58. Saiwai H, Ohkawa Y, Yamada H, Kumamaru H, Harada A, Okano H, Yokomizo T, Iwamoto Y, Okada S. The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury. Am J Pathol. 2010;176(5):2352–66. doi:10.2353/ajpath.2010.090839.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Rios-Santos F, Benjamim CF, Zavery D, Ferreira SH, Cunha Fde Q. A critical role of leukotriene B4 in neutrophil migration to infectious focus in cecal ligation and puncture sepsis. Shock. 2003;19(1):61–5.

    Article  CAS  PubMed  Google Scholar 

  60. Hayashi F, Means TK, Luster AD. Toll-like receptors stimulate human neutrophil function. Blood. 2003;102(7):2660–9. doi:10.1182/blood-2003-04-1078.

    Article  CAS  PubMed  Google Scholar 

  61. Akira S. TLR signaling. Curr Top Microbiol Immunol. 2006;311:1–16.

    CAS  PubMed  Google Scholar 

  62. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007;81(1):1–5. doi:10.1189/jlb.0306164.

    Article  CAS  PubMed  Google Scholar 

  63. Speca S, Giusti I, Rieder F, Latella G. Cellular and molecular mechanisms of intestinal fibrosis. World J Gastroenterol. 2012;18(28):3635–61. doi:10.3748/wjg.v18.i28.3635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Amano MT, Camara NO. The immunomodulatory role of carbon monoxide during transplantation. Med Gas Res. 2013;3(1):1. doi:10.1186/2045-9912-3-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Castoldi A, Braga TT, Correa-Costa M, Aguiar CF, Bassi EJ, Correa-Silva R, Elias RM, Salvador F, Moraes-Vieira PM, Cenedeze MA, Reis MA, Hiyane MI, Pacheco-Silva A, Goncalves GM, Saraiva Camara NO. TLR2, TLR4 and the MYD88 signaling pathway are crucial for neutrophil migration in acute kidney injury induced by sepsis. PLoS One. 2012;7(5):e37584. doi:10.1371/journal.pone.0037584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Fan J, Malik AB. Toll-like receptor-4 (TLR4) signaling augments chemokine-induced neutrophil migration by modulating cell surface expression of chemokine receptors. Nat Med. 2003;9(3):315–21. doi:10.1038/nm832.

    Article  CAS  PubMed  Google Scholar 

  67. Opal SM, Laterre PF, Francois B, LaRosa SP, Angus DC, Mira JP, Wittebole X, Dugernier T, Perrotin D, Tidswell M, Jauregui L, Krell K, Pachl J, Takahashi T, Peckelsen C, Cordasco E, Chang CS, Oeyen S, Aikawa N, Maruyama T, Schein R, Kalil AC, Van Nuffelen M, Lynn M, Rossignol DP, Gogate J, Roberts MB, Wheeler JL, Vincent JL, AS Group. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA. 2013;309(11):1154–62. doi:10.1001/jama.2013.2194.

    Article  CAS  PubMed  Google Scholar 

  68. Patial S, Saini Y, Parvataneni S, Appledorn DM, Dorn GW 2nd, Lapres JJ, Amalfitano A, Senagore P, Parameswaran N. Myeloid-specific GPCR kinase-2 negatively regulates NF-kappaB1p105-ERK pathway and limits endotoxemic shock in mice. J Cell Physiol. 2011;226(3):627–37. doi:10.1002/jcp.22384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bauer S, Kirschning CJ, Hacker H, Redecke V, Hausmann S, Akira S, Wagner H, Lipford GB. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA. 2001;98(16):9237–42. doi:10.1073/pnas.161293498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hemmi H, Kaisho T, Takeda K, Akira S. The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets. J Immunol. 2003;170(6):3059–64.

    Article  CAS  PubMed  Google Scholar 

  71. Martin-Armas M, Simon-Santamaria J, Pettersen I, Moens U, Smedsrod B, Sveinbjornsson B. Toll-like receptor 9 (TLR9) is present in murine liver sinusoidal endothelial cells (LSECs) and mediates the effect of CpG-oligonucleotides. J Hepatol. 2006;44(5):939–46. doi:10.1016/j.jhep.2005.09.020.

    Article  CAS  PubMed  Google Scholar 

  72. Bhan U, Lukacs NW, Osterholzer JJ, Newstead MW, Zeng X, Moore TA, McMillan TR, Krieg AM, Akira S, Standiford TJ. TLR9 is required for protective innate immunity in Gram-negative bacterial pneumonia: role of dendritic cells. J Immunol. 2007;179(6):3937–46.

    Article  CAS  PubMed  Google Scholar 

  73. Plitas G, Burt BM, Nguyen HM, Bamboat ZM, DeMatteo RP. Toll-like receptor 9 inhibition reduces mortality in polymicrobial sepsis. J Exp Med. 2008;205(6):1277–83. doi:10.1084/jem.20080162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Roh YS, Zhang B, Loomba R, Seki E. TLR2 and TLR9 contribute to alcohol-mediated liver injury through induction of CXCL1 and neutrophil infiltration. Am J Physiol Gastrointest Liver Physiol. 2015;309(1):G30–41. doi:10.1152/ajpgi.00031.2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. O’Neill LA, Dinarello CA. The IL-1 receptor/toll-like receptor superfamily: crucial receptors for inflammation and host defense. Immunol Today. 2000;21(5):206–9.

    Article  PubMed  Google Scholar 

  76. Secher T, Vasseur V, Poisson DM, Mitchell JA, Cunha FQ, Alves-Filho JC, Ryffel B. Crucial role of TNF receptors 1 and 2 in the control of polymicrobial sepsis. J Immunol. 2009;182(12):7855–64. doi:10.4049/jimmunol.0804008.

    Article  CAS  PubMed  Google Scholar 

  77. Weichhart T, Saemann MD. The PI3 K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications. Ann Rheum Dis. 2008;67(Suppl 3):iii70–4. doi:10.1136/ard.2008.098459.

    Article  CAS  PubMed  Google Scholar 

  78. Coxon PY, Rane MJ, Uriarte S, Powell DW, Singh S, Butt W, Chen Q, McLeish KR. MAPK-activated protein kinase-2 participates in p38 MAPK-dependent and ERK-dependent functions in human neutrophils. Cell Signal. 2003;15(11):993–1001.

    Article  CAS  PubMed  Google Scholar 

  79. Feng Y, Zou L, Zhang M, Li Y, Chen C, Chao W. MyD88 and Trif signaling play distinct roles in cardiac dysfunction and mortality during endotoxin shock and polymicrobial sepsis. Anesthesiology. 2011;115(3):555–67. doi:10.1097/ALN.0b013e31822a22f7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Deng JC, Cheng G, Newstead MW, Zeng X, Kobayashi K, Flavell RA, Standiford TJ. Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M. J Clin Invest. 2006;116(9):2532–42. doi:10.1172/JCI28054.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Otsuka Y, Nagano K, Nagano K, Hori K, Oh-ishi J, Hayashi H, Watanabe N, Niitsu Y. Inhibition of neutrophil migration by tumor necrosis factor. Ex vivo and in vivo studies in comparison with in vitro effect. J Immunol. 1990;145(8):2639–43.

    CAS  PubMed  Google Scholar 

  82. Cunha FQ, Assreuy J, Moss DW, Rees D, Leal LM, Moncada S, Carrier M, O’Donnell CA, Liew FY. Differential induction of nitric oxide synthase in various organs of the mouse during endotoxemia: role of TNF-alpha and IL-1-beta. Immunology. 1994;81(2):211–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Roy S, Sharma S, Sharma M, Bose M. Differential signaling of inducible nitric oxide synthase induction in Mycobacterium tuberculosis infected alveolar epithelial cell line A549 in response to cytokines IFN-gamma, TNF-alpha and IL-1beta. Int J Mycobacteriol. 2014;3(1):17–24. doi:10.1016/j.ijmyco.2014.01.008.

    Article  PubMed  Google Scholar 

  84. Benjamim CF, Ferreira SH, Cunha FQ. Role of nitric oxide in the failure of neutrophil migration in sepsis. J Infect Dis. 2000;182(1):214–23. doi:10.1086/315682.

    Article  CAS  PubMed  Google Scholar 

  85. Wang L, Taneja R, Razavi HM, Law C, Gillis C, Mehta S. Specific role of neutrophil inducible nitric oxide synthase in murine sepsis-induced lung injury in vivo. Shock. 2012;37(5):539–47. doi:10.1097/SHK.0b013e31824dcb5a.

    Article  CAS  PubMed  Google Scholar 

  86. 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. Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med. 2010;16(6):708–12. doi:10.1038/nm.2156.

    Article  CAS  PubMed  Google Scholar 

  87. Le HT, Tran VG, Kim W, Kim J, Cho HR, Kwon B. IL-33 priming regulates multiple steps of the neutrophil-mediated anti-Candida albicans response by modulating TLR and dectin-1 signals. J Immunol. 2012;189(1):287–95. doi:10.4049/jimmunol.1103564.

    Article  CAS  PubMed  Google Scholar 

  88. Ferreira AE, Sisti F, Sonego F, Wang S, Filgueiras LR, Brandt S, Serezani AP, Du H, Cunha FQ, Alves-Filho JC, Serezani CH. PPAR-gamma/IL-10 axis inhibits MyD88 expression and ameliorates murine polymicrobial sepsis. J Immunol. 2014;192(5):2357–65. doi:10.4049/jimmunol.1302375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lerman YV, Kim M. Neutrophil migration under normal and sepsis conditions. Cardiovasc Hematol Disord Drug Targets. 2015;15(1):19–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kovach MA, Standiford TJ. The function of neutrophils in sepsis. Curr Opin Infect Dis. 2012;25(3):321–7. doi:10.1097/QCO.0b013e3283528c9b.

    Article  CAS  PubMed  Google Scholar 

  91. Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006;6(3):173–82. doi:10.1038/nri1785.

    Article  CAS  PubMed  Google Scholar 

  92. Cassatella MA. The neutrophil: one of the cellular targets of interleukin-10. Int J Clin Lab Res. 1998;28(3):148–61.

    Article  CAS  PubMed  Google Scholar 

  93. Crepaldi L, Gasperini S, Lapinet JA, Calzetti F, Pinardi C, Liu Y, Zurawski S, de Waal Malefyt R, Moore KW, Cassatella MA. Up-regulation of IL-10R1 expression is required to render human neutrophils fully responsive to IL-10. J Immunol. 2001;167(4):2312–22.

    Article  CAS  PubMed  Google Scholar 

  94. Bazzoni F, Tamassia N, Rossato M, Cassatella MA. Understanding the molecular mechanisms of the multifaceted IL-10-mediated anti-inflammatory response: lessons from neutrophils. Eur J Immunol. 2010;40(9):2360–8. doi:10.1002/eji.200940294.

    Article  CAS  PubMed  Google Scholar 

  95. Bhattacharyya S, Sen P, Wallet M, Long B, Baldwin AS Jr, Tisch R. Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3 K/Akt pathway and of IkappaB kinase activity. Blood. 2004;104(4):1100–9. doi:10.1182/blood-2003-12-4302.

    Article  CAS  PubMed  Google Scholar 

  96. Carlow DA, Gossens K, Naus S, Veerman KM, Seo W, Ziltener HJ. PSGL-1 function in immunity and steady state homeostasis. Immunol Rev. 2009;230(1):75–96. doi:10.1111/j.1600-065X.2009.00797.x.

    Article  CAS  PubMed  Google Scholar 

  97. Katayama Y, Hidalgo A, Chang J, Peired A, Frenette PS. CD44 is a physiological E-selectin ligand on neutrophils. J Exp Med. 2005;201(8):1183–9. doi:10.1084/jem.20042014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Hidalgo A, Peired AJ, Wild MK, Vestweber D, Frenette PS. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44. Immunity. 2007;26(4):477–89. doi:10.1016/j.immuni.2007.03.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Schymeinsky J, Mocsai A, Walzog B. Neutrophil activation via beta2 integrins (CD11/CD18): molecular mechanisms and clinical implications. Thromb Haemost. 2007;98(2):262–73.

    CAS  PubMed  Google Scholar 

  100. Laudanna C, Kim JY, Constantin G, Butcher E. Rapid leukocyte integrin activation by chemokines. Immunol Rev. 2002;186:37–46.

    Article  CAS  PubMed  Google Scholar 

  101. Napimoga MH, Vieira SM, Dal-Secco D, Freitas A, Souto FO, Mestriner FL, Alves-Filho JC, Grespan R, Kawai T, Ferreira SH, Cunha FQ. Peroxisome proliferator-activated receptor-gamma ligand, 15-deoxy-Delta 12,14-prostaglandin J2, reduces neutrophil migration via a nitric oxide pathway. J Immunol. 2008;180(1):609–17.

    Article  CAS  PubMed  Google Scholar 

  102. Reddy RC, Narala VR, Keshamouni VG, Milam JE, Newstead MW, Standiford TJ. Sepsis-induced inhibition of neutrophil chemotaxis is mediated by activation of peroxisome proliferator-activated receptor-{gamma}. Blood. 2008;112(10):4250–8. doi:10.1182/blood-2007-12-128967.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Taye A, El-Sheikh AA. Lectin-like oxidized low-density lipoprotein receptor 1 pathways. Eur J Clin Invest. 2013;43(7):740–5. doi:10.1111/eci.12092.

    Article  CAS  PubMed  Google Scholar 

  104. Takanabe-Mori R, Ono K, Wada H, Takaya T, Ura S, Yamakage H, Satoh-Asahara N, Shimatsu A, Takahashi Y, Fujita M, Fujita Y, Sawamura T, Hasegawa K. Lectin-like oxidized low-density lipoprotein receptor-1 plays an important role in vascular inflammation in current smokers. J Atheroscler Thromb. 2013;20(6):585–90.

    Article  CAS  PubMed  Google Scholar 

  105. Dunn S, Vohra RS, Murphy JE, Homer-Vanniasinkam S, Walker JH, Ponnambalam S. The lectin-like oxidized low-density-lipoprotein receptor: a pro-inflammatory factor in vascular disease. Biochem J. 2008;409(2):349–55. doi:10.1042/BJ20071196.

    Article  CAS  PubMed  Google Scholar 

  106. Apte RN, Dotan S, Elkabets M, White MR, Reich E, Carmi Y, Song X, Dvozkin T, Krelin Y, Voronov E. The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev. 2006;25(3):387–408. doi:10.1007/s10555-006-9004-4.

    Article  CAS  PubMed  Google Scholar 

  107. Everhart MB, Han W, Sherrill TP, Arutiunov M, Polosukhin VV, Burke JR, Sadikot RT, Christman JW, Yull FE, Blackwell TS. Duration and intensity of NF-kappaB activity determine the severity of endotoxin-induced acute lung injury. J Immunol. 2006;176(8):4995–5005.

    Article  CAS  PubMed  Google Scholar 

  108. Shimaoka T, Kume N, Minami M, Hayashida K, Sawamura T, Kita T, Yonehara S. LOX-1 supports adhesion of Gram-positive and Gram-negative bacteria. J Immunol. 2001;166(8):5108–14.

    Article  CAS  PubMed  Google Scholar 

  109. Wu Z, Sawamura T, Kurdowska AK, Ji HL, Idell S, Fu J. LOX-1 deletion improves neutrophil responses, enhances bacterial clearance, and reduces lung injury in a murine polymicrobial sepsis model. Infect Immun. 2011;79(7):2865–70. doi:10.1128/IAI.01317-10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Foundation of China, No. 81071546, No. 81272148 and No. 81471903; by the Jiangsu Natural Science Foundation, No. BK2012703.

Author information

Authors and Affiliations

  1. Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, 212001, Jiangsu, China

    Huafeng Zhang & Bingwei Sun

Authors
  1. Huafeng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bingwei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bingwei Sun.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Additional information

Responsible Editor: John Di Battista.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, H., Sun, B. Pleiotropic regulations of neutrophil receptors response to sepsis. Inflamm. Res. 66, 197–207 (2017). https://doi.org/10.1007/s00011-016-0993-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-016-0993-3

Keywords

Search

Navigation