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Inflammation Research

, Volume 61, Issue 9, pp 931–939 | Cite as

Two circulating neutrophil populations in acute inflammation in mice

  • Hildur H. Arnardottir
  • Jona Freysdottir
  • Ingibjorg HardardottirEmail author
Original Research Paper

Abstract

Objective and design

Recent studies indicate that neutrophils are heterogeneous and may have an immunosuppressive role in addition to their well-known phagocytic and bactericidal function. This study examined neutrophil subpopulations in the circulation, peritoneum, spleen and bone marrow from mice at various time points after induction of acute inflammation.

Material, treatment and methods

Female C57BL/6 mice were injected intraperitoneally with lipopolysaccharide (LPS). Blood, peritoneal, spleen and bone marrow cells were collected and counted and expression of surface molecules and chemokine receptors analyzed with flow cytometry. Chemokine and cytokine concentrations in serum and peritoneal fluid were determined by ELISA.

Results

Neutrophil numbers in the circulation decreased following administration of LPS but reached similar numbers to those prior to inflammation at 8 h. At that time point, two distinct neutrophil populations were present in the circulation. These two neutrophil populations differed in size, granularity and expression of CD11b and Ly6G. Few neutrophils were recruited into the peritoneum until 24 h after administration of LPS at a time when the neutrophils in the circulation had increased their expression of the chemokine receptor CXCR2.

Conclusions

Induction of acute inflammation leads to the appearance of two circulating neutrophil subpopulations, which may differ in their activation state and function.

Keywords

Neutrophil subpopulations Lipopolysaccharide Mice Inflammation 

Notes

Acknowledgments

The authors would like to thank Dr. M. Mack for providing an antibody against CCR2 for this study. This project was supported by grants from the Icelandic Research Fund and the University of Iceland Research Fund.

References

  1. 1.
    Opal SM. Endotoxins and other sepsis triggers. Contrib Nephrol. 2010;167:14–24.PubMedCrossRefGoogle Scholar
  2. 2.
    Frazier WJ, Hall MW. Immunoparalysis and adverse outcomes from critical illness. Pediatr Clin North Am. 2008;55:647–68. (xi).PubMedCrossRefGoogle Scholar
  3. 3.
    Seki E, Tsutsui H, Tsuji NM, Hayashi N, Adachi K, Nakano H, et al. Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice. J Immunol. 2002;169:3863–8.PubMedGoogle Scholar
  4. 4.
    Aderem AA, Rosen A, Barker KA. Modulation of prostaglandin and leukotriene biosynthesis. Curr Opin Immunol. 1988;1:56–62.PubMedCrossRefGoogle Scholar
  5. 5.
    Kasten KR, Muenzer JT, Caldwell CC. Neutrophils are significant producers of IL-10 during sepsis. Biochem Biophys Res Commun. 2010;393:28–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Zhang X, Majlessi L, Deriaud E, Leclerc C, Lo-Man R. Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. Immunity. 2009;31:761–71.PubMedCrossRefGoogle Scholar
  7. 7.
    Davey MS, Tamassia N, Rossato M, Bazzoni F, Calzetti F, Bruderek K, et al. Failure to detect production of IL-10 by activated human neutrophils. Nat Immunol; 12:1017-8; author reply 1018–20.Google Scholar
  8. 8.
    Pillay J, Kamp VM, van Hoffen E, Visser T, Tak T, Lammers JW, et al. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. J Clin Invest. 2012;122:327–36.PubMedCrossRefGoogle Scholar
  9. 9.
    Pillay J, Ramakers BP, Kamp VM, Loi AL, Lam SW, Hietbrink F, et al. Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 2010;88:211–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Abi Abdallah DS, Egan CE, Butcher BA, Denkers EY. Mouse neutrophils are professional antigen-presenting cells programmed to instruct Th1 and Th17 T-cell differentiation. Int Immunol. 2011;23:317–26.PubMedCrossRefGoogle Scholar
  11. 11.
    Dahlgren C, Karlsson A, Sendo F. Neutrophil secretory vesicles are the intracellular reservoir for GPI-80, a protein with adhesion-regulating potential. J Leukoc Biol. 2001;69:57–62.PubMedGoogle Scholar
  12. 12.
    Kishimoto TK, Jutila MA, Berg EL, Butcher EC. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science. 1989;245:1238–41.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu JJ, Song CW, Yue Y, Duan CG, Yang J, He T, et al. Quercetin inhibits LPS-induced delay in spontaneous apoptosis and activation of neutrophils. Inflamm Res. 2005;54:500–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Bouabe H, Liu Y, Moser M, Bosl MR, Heesemann J. Novel highly sensitive IL-10-beta-lactamase reporter mouse reveals cells of the innate immune system as a substantial source of IL-10 in vivo. J Immunol. 2011;187:3165–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Noel G, Wang Q, Schwemberger S, Hanson C, Giacalone N, Haar L, et al. Neutrophils, not monocyte/macrophages, are the major splenic source of postburn IL-10. Shock. 2011;36:149–55.PubMedCrossRefGoogle Scholar
  16. 16.
    Burdon PC, Martin C, Rankin SM. Migration across the sinusoidal endothelium regulates neutrophil mobilization in response to ELR + CXC chemokines. Br J Haematol. 2008;142:100–8.PubMedCrossRefGoogle Scholar
  17. 17.
    McAvoy EF, McDonald B, Parsons SA, Wong CH, Landmann R, Kubes P. The role of CD14 in neutrophil recruitment within the liver microcirculation during endotoxemia. J Immunol. 2011;186:2592–601.PubMedCrossRefGoogle Scholar
  18. 18.
    Erzurum SC, Downey GP, Doherty DE, Schwab B 3rd, Elson EL, Worthen GS. Mechanisms of lipopolysaccharide-induced neutrophil retention. Relative contributions of adhesive and cellular mechanical properties. J Immunol. 1992;149:154–62.PubMedGoogle Scholar
  19. 19.
    Andonegui G, Bonder CS, Green F, Mullaly SC, Zbytnuik L, Raharjo E, et al. Endothelium-derived Toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs. J Clin Invest. 2003;111:1011–20.PubMedGoogle Scholar
  20. 20.
    Haziot A, Hijiya N, Gangloff SC, Silver J, Goyert SM. Induction of a novel mechanism of accelerated bacterial clearance by lipopolysaccharide in CD14-deficient and Toll-like receptor 4-deficient mice. J Immunol. 2001;166:1075–8.PubMedGoogle Scholar
  21. 21.
    Rao TS, Currie JL, Shaffer AF, Isakson PC. In vivo characterization of zymosan-induced mouse peritoneal inflammation. J Pharmacol Exp Ther. 1994;269:917–25.PubMedGoogle Scholar
  22. 22.
    Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, Morrill-Labrode A, et al. Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr. 1991;121:547–55.PubMedGoogle Scholar
  23. 23.
    Goncalves AS, Appelberg R. The involvement of the chemokine receptor CXCR2 in neutrophil recruitment in LPS-induced inflammation and in Mycobacterium avium infection. Scand J Immunol. 2002;55:585–91.PubMedCrossRefGoogle Scholar
  24. 24.
    Rios-Santos F, Alves-Filho JC, Souto FO, Spiller F, Freitas A, Lotufo CM, et al. 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;175:490–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Khandaker MH, Xu L, Rahimpour R, Mitchell G, DeVries ME, Pickering JG, et al. CXCR1 and CXCR2 are rapidly down-modulated by bacterial endotoxin through a unique agonist-independent, tyrosine kinase-dependent mechanism. J Immunol. 1998;161:1930–8.PubMedGoogle Scholar
  26. 26.
    Rose JJ, Foley JF, Murphy PM, Venkatesan S. On the mechanism and significance of ligand-induced internalization of human neutrophil chemokine receptors CXCR1 and CXCR2. J Biol Chem. 2004;279:24372–86.PubMedCrossRefGoogle Scholar
  27. 27.
    Khandaker MH, Mitchell G, Xu L, Andrews JD, Singh R, Leung H, et al. Metalloproteinases are involved in lipopolysaccharide- and tumor necrosis factor-alpha-mediated regulation of CXCR1 and CXCR2 chemokine receptor expression. Blood. 1999;93:2173–85.PubMedGoogle Scholar
  28. 28.
    McColl SR, Clark-Lewis I. Inhibition of murine neutrophil recruitment in vivo by CXC chemokine receptor antagonists. J Immunol. 1999;163:2829–35.PubMedGoogle Scholar
  29. 29.
    Tessier PA, Naccache PH, Clark-Lewis I, Gladue RP, Neote KS, McColl SR. Chemokine networks in vivo: involvement of C-X-C and C–C chemokines in neutrophil extravasation in vivo in response to TNF-alpha. J Immunol. 1997;159:3595–602.PubMedGoogle Scholar
  30. 30.
    Witowski J, Ksiazek K, Warnecke C, Kuzlan M, Korybalska K, Tayama H, et al. Role of mesothelial cell-derived granulocyte colony-stimulating factor in interleukin-17-induced neutrophil accumulation in the peritoneum. Kidney Int. 2007;71:514–25.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Hildur H. Arnardottir
    • 1
    • 3
  • Jona Freysdottir
    • 2
    • 3
  • Ingibjorg Hardardottir
    • 1
    Email author
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of IcelandReykjavikIceland
  2. 2.Department of Immunology, Faculty of Medicine, Biomedical CenterUniversity of IcelandReykjavikIceland
  3. 3.Center of Rheumatology Research and Department of ImmunologyLandspitali – The National University Hospital of IcelandReykjavikIceland

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