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Stage-dependent detection of CD14+ and CD16+ cells in the human heart after myocardial infarction

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Abstract

Monocytes are critically involved in cardiovascular wound healing processes. Human monocytes can be classified into two subsets based on the expression of CD14 and CD16. Here, we examined the temporal and spatial distribution of CD14+ and CD16+ cells after myocardial infarction (MI) in human heart and spleen tissue and correlated it with markers of cardiac repair. Heart samples obtained at autopsy were histologically classified into acute (AMI; n = 11), subacute (SAMI; n = 10) and old (OMI; n = 16) MI, or control myocardium (CONTR; n = 8). Histochemical analyses revealed marked fibrosis in OMI (p < 0.001 vs. CONTR). The adhesion molecule CD56 was also strongly expressed in OMI (p < 0.01 vs. CONTR) and found to correlate with fibrosis (p < 0.001). The number of capillaries was reduced in OMI (p < 0.01 vs. CONTR; p < 0.05 vs. AMI), whereas the hypoxia indicator carbonic anhydrase IX was predominantly expressed in AMI (p < 0.01 vs. OMI and CONTR) and SAMI (p < 0.05 vs. OMI and CONTR). The monocyte chemoattractrant osteopontin was also more highly expressed in hearts of SAMI patients (p < 0.01 vs. CONTR). Numbers of CD14+ monocytes were found to correlate with CD16+ cells (p < 0.05) and inversely with fibrosis (p < 0.05). Regarding a MI-associated release of monocytes from spleen reservoirs, a non-significant reduction of splenic CD14+ and CD16+ cells was detected in subjects with AMI. In conclusion, disease stage-specific alterations in CD14+ and CD16+ cells in human heart may contribute to cardiac repair processes following MI.

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References

  1. Petersen S, Peto V, Rayner K, Leal J, Luengo-Fernandez R, Gray A (2005) European cardiovascular disease statistics. British Heart Foundation, London

    Google Scholar 

  2. Nahrendorf M, Swirski FK, Aikawa E et al (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204:3037–3047

    Article  PubMed  CAS  Google Scholar 

  3. Nahrendorf M, Pittet MJ, Swirski FK (2007) Monocytes: protagonists of infarct inflammation and repair after myocardial infarction. Circulation 121:2437–2445

    Article  Google Scholar 

  4. Auffray C, Sieweke MH, Geissmann F (2009) Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 27:669–692

    Article  PubMed  CAS  Google Scholar 

  5. Passlick B, Flieger D, Ziegler-Heitbrock HW (1989) Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 74:2527–2534

    PubMed  CAS  Google Scholar 

  6. Rogacev KS, Ulrich C, Blomer L et al (2010) Monocyte heterogeneity in obesity and subclinical atherosclerosis. Eur Heart J 31:369–376

    Article  PubMed  CAS  Google Scholar 

  7. Schlitt A, Heine GH, Blankenberg S et al (2004) CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels. Thromb Haemost 92:419–424

    PubMed  CAS  Google Scholar 

  8. Tsujioka H, Imanishi T, Ikejima H et al (2009) Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. J Am Coll Cardiol 54:130–138

    Article  PubMed  Google Scholar 

  9. Tsujioka H, Imanishi T, Ikejima H et al (2010) Post-reperfusion enhancement of CD14(+)CD16(−) monocytes and microvascular obstruction in ST-segment elevation acute myocardial infarction. Circ J 74:1175–1182

    Article  PubMed  Google Scholar 

  10. Swirski FK, Nahrendorf M, Etzrodt M et al (2009) Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325:612–616

    Article  PubMed  CAS  Google Scholar 

  11. Cotran RS, Kumar V, Collins T (1999) Robbins pathologic basis of disease, 6th edn. Saunders, Philadelphia

    Google Scholar 

  12. Swirski FK, Weissleder R, Pittet MJ (2009) Heterogeneous in vivo behavior of monocyte subsets in atherosclerosis. Arterioscler Thromb Vasc Biol 29:1424–1432

    Article  PubMed  CAS  Google Scholar 

  13. Nagao K, Ono K, Iwanaga Y et al (2010) Neural cell adhesion molecule is a cardioprotective factor up-regulated by metabolic stress. J Mol Cell Cardiol 48:1157–1168

    Article  PubMed  CAS  Google Scholar 

  14. Wykoff CC, Beasley NJ, Watson PH et al (2000) Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res 60:7075–7083

    PubMed  CAS  Google Scholar 

  15. Duvall CL, Weiss D, Robinson ST et al (2008) The role of osteopontin in recovery from hind limb ischemia. Arterioscler Thromb Vasc Biol 28:290–295

    Article  PubMed  CAS  Google Scholar 

  16. van Amerongen MJ, Harmsen MC, van Rooijen N et al (2007) Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. Am J Pathol 170:818–829

    Article  PubMed  Google Scholar 

  17. Frangogiannis NG, Mendoza LH, Ren G et al (2003) MCSF expression is induced in healing myocardial infarcts and may regulate monocyte and endothelial cell phenotype. Am J Physiol Heart Circ Physiol 285:H483–H492

    PubMed  CAS  Google Scholar 

  18. Yano T, Miura T, Whittaker P et al (2006) Macrophage colony-stimulating factor treatment after myocardial infarction attenuates left ventricular dysfunction by accelerating infarct repair. J Am Coll Cardiol 47:626–634

    Article  PubMed  CAS  Google Scholar 

  19. van der Laan AM, Hirsch A, Robbers LF et al (2012) A proinflammatory monocyte response is associated with myocardial injury and impaired functional outcome in patients with ST-segment elevation myocardial infarction: monocytes and myocardial infarction. Am Heart J 163:57–65

    Article  PubMed  Google Scholar 

  20. Ikejima H, Imanishi T, Tsujioka H et al (2010) Effect of human peripheral monocyte subsets on coronary flow reserve in infarct-related artery in patients with primary anterior acute myocardial infarction. Clin Exp Pharmacol Physiol 37:453–459

    Article  PubMed  CAS  Google Scholar 

  21. Nitta T, Yagita H, Sato K et al (1989) Involvement of CD56 (NKH-1/Leu-19 antigen) as an adhesion molecule in natural killer-target cell interaction. J Exp Med 170:1757–1761

    Article  PubMed  CAS  Google Scholar 

  22. Husser O, Bodi V, Sanchis J et al (2011) White blood cell subtypes after STEMI: temporal evolution, association with cardiovascular magnetic resonance—derived infarct size and impact on outcome. Inflammation 34:73–84

    Article  PubMed  Google Scholar 

  23. Leuschner F, Rauch PJ, Ueno T et al (2012) Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis. J Exp Med 209:123–137

    Article  PubMed  CAS  Google Scholar 

  24. Robinette CD, Fraumeni JF Jr (1977) Splenectomy and subsequent mortality in veterans of the 1939–45 war. Lancet 2:127–129

    Article  PubMed  CAS  Google Scholar 

  25. Montet-Abou K, Daire JL, Hyacinthe JN et al (2010) In vivo labelling of resting monocytes in the reticuloendothelial system with fluorescent iron oxide nanoparticles prior to injury reveals that they are mobilized to infarcted myocardium. Eur Heart J 31:1410–1420

    Article  PubMed  CAS  Google Scholar 

  26. Dutta P, Courties G, Wei Y et al (2012) Myocardial infarction accelerates atherosclerosis. Nature 487:325–329

    Article  PubMed  CAS  Google Scholar 

  27. Dobaczewski M, Gonzalez-Quesada C, Frangogiannis NG (2010) The extracellular matrix as a modulation of the inflammatory and reparative response following myocardial infarction. J Mol Cell Cardiol 48:504–511

    Article  PubMed  CAS  Google Scholar 

  28. Wittig B, Seiter S, Schmidt DS et al (1999) CD44 variant isoforms on blood leukocytes in chronic inflammatory bowel disease and other systemic autoimmune diseases. Lab Investig 79:747–759

    PubMed  CAS  Google Scholar 

  29. Zhao X, Johnson JN, Singh K et al (2007) Impairment of myocardial angiogenic response in the absence of osteopontin. Microcirculation 14:233–240

    Article  PubMed  CAS  Google Scholar 

  30. Trueblood NA, Xie Z, Communal C et al (2001) Exaggerated left ventricular dilation and reduced collagen deposition after myocardial infarction in mice lacking osteopontin. Circ Res 88:1080–1087

    Article  PubMed  CAS  Google Scholar 

  31. Doherty P, Ashton SV, Moore SE et al (1991) Morphoregulatory activities of NCAM and N-cadherin can be accounted for by G protein-dependent activation of L- and N-type neuronal Ca2+ channels. Cell 67:21–33

    Article  PubMed  CAS  Google Scholar 

  32. Gattenlohner S, Waller C, Ertl G et al (2003) NCAM(CD56) and RUNX1(AML1) are up-regulated in human ischemic cardiomyopathy and a rat model of chronic cardiac ischemia. Am J Pathol 163:1081–1090

    Article  PubMed  Google Scholar 

  33. Wohlschlaeger J, von Winterfeld M, Milting H et al (2008) Decreased myocardial chromogranin a expression and colocalization with brain natriuretic peptide during reverse cardiac remodeling after ventricular unloading. J Heart Lung Transplant 27:442–449

    Article  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Mercedes Martin-Ortega for expert technical assistance. This work was supported by a Heidenreich von Siebold-Programm 2010 grant of the University Medical Center Göttingen (to F.S.C.).

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The authors declare that they have no conflict of interest.

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Correspondence to Katrin Schäfer.

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Czepluch, F.S., Schlegel, M., Bremmer, F. et al. Stage-dependent detection of CD14+ and CD16+ cells in the human heart after myocardial infarction. Virchows Arch 463, 459–469 (2013). https://doi.org/10.1007/s00428-013-1447-8

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  • DOI: https://doi.org/10.1007/s00428-013-1447-8

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