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Soluble form of the endothelial adhesion molecule CD146 binds preferentially CD16+ monocytes

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Abstract

The cell adhesion molecule CD146 is normally located at the endothelial cell-to-cell junction and colocalizes with actin cytoskeleton. The soluble form of CD146 (sCD146) has been identified in the endothelial cell supernatant and in normal human plasma, and is increased in pathologic conditions with altered endothelial function. Soluble CD146 binding to monocytes promotes their transendothelial migration, which represents a central step in the development of atherosclerotic plaque. Since peripheral blood monocytes are characterized by a phenotypic and functional heterogeneity, with different transendothelial migration capacity, we hypothesized that monocyte subsets differently bind sCD146. Based on surface CD14 and CD16 expression monocytes were distinguished by flow cytometry (FACS) into three subsets: CD14++/CD16−, CD14++/CD16+ and CD14+/CD16+. CD16+ monocytes have been found to possess higher transendothelial migration ability. FACS analysis on blood monocytes from 30 healthy subjects revealed that higher percentages of CD14++/CD16+ (median, first and third quartile: 2.26, 1.62–3.87) and of CD14+/CD16+ (2.59, 1.28–4.80) were positive for CD146 (both p < 0.01), in comparison to CD14++/CD16− (0.66, 0.47–1.01). Moreover, in vitro treatment of ficoll separated monocytes with recombinant CD146 showed that both CD16+ subsets increased their percentage of CD146-positive events compared to CD16− monocytes (p < 0.01). Soluble CD146 levels were evaluated by ELISA in plasma samples of subjects from our study group and showed a correlation with percentage of CD146-positive CD14+/CD16+ monocyte subset. In this work we have demonstrated that monocyte subsets behave differently with regard to their sCD146 binding activity; because binding of CD146 influences transendothelial migration of monocytes, modulation of monocyte-CD146 interaction may represent a potential target to limit atherosclerotic plaque development.

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References

  1. Cines D, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM (1998) Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91:3527–3561

    PubMed  CAS  Google Scholar 

  2. Lampugnani MG, Dejana E (1997) Interendothelial junctions: structure, signalling and functional roles. Curr Opin Cell Biol 9:674–682

    Article  PubMed  CAS  Google Scholar 

  3. Bazzoni G, Dejana E (2004) Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84:869–901

    Article  PubMed  CAS  Google Scholar 

  4. Dejana E (2004) Endothelial cell–cell junctions: happy together. Natl Rev Mol Cell Biol 5:261–270

    Article  CAS  Google Scholar 

  5. Albelda SM, Muller WA, Buck CA, Newman PJ (1991) Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell–cell adhesion molecule. J Cell Biol 114:1059–1068

    Article  PubMed  CAS  Google Scholar 

  6. Solovey AN, Gui L, Chang L, Enenstein J, Browne PV, Hebbel RP (2001) Identification and functional assessment of endothelial P1H12. J Lab Clin Med 138:322–331

    Article  PubMed  CAS  Google Scholar 

  7. Bardin N, Francès V, Lesaule G, Horschowski N, George F, Sampol J (1996) Identification of the S-Endo 1 endothelial-associated antigen. Biochem Biophys Res Commun 218:210–216

    Article  PubMed  CAS  Google Scholar 

  8. Shih IM (1999) The role of CD146 (Mel-CAM) in biology and pathology. J Pathol 189:4–11

    Article  PubMed  CAS  Google Scholar 

  9. Bardin N, Anfosso F, Massé JM, Cramer E, Sabatier F, Le Bivic A, Sampol J, Dignat-George F (2001) Identification of CD146 as a component of the endothelial junction involved in the control of cell–cell cohesion. Blood 98:3677–3684

    Article  PubMed  CAS  Google Scholar 

  10. Anfosso F, Bardin N, Vivier E, Sabatier F, Sampol J, Dignat-George F (2001) Outside-in signaling pathway linked to CD146 engagement in human endothelial cells. J Biol Chem 276:1564–1569

    Article  PubMed  CAS  Google Scholar 

  11. Meydani M (2003) Soluble adhesion molecules: surrogate markers of cardiovascular disease? Nutr Rev 61:63–68

    Article  PubMed  Google Scholar 

  12. Blankenberg S, Barbaux S, Tiret L (2003) Adhesion molecules and atherosclerosis. Atherosclerosis 170:191–203

    Article  PubMed  CAS  Google Scholar 

  13. Bardin N, Francès V, Combes V, Sampol J, Dignat-George F (1998) CD146: biosynthesis and production of a soluble form in human cultured endothelial cells. FEBS Lett 421:12–14

    Article  PubMed  CAS  Google Scholar 

  14. Bardin N, Moal V, Anfosso F, Daniel L, Brunet P, Sampol J, Dignat George F (2003) Soluble CD146, a novel endothelial marker, is increased in physiopathological settings linked to endothelial junctional alteration. Thromb Haemost 90:915–920

    PubMed  CAS  Google Scholar 

  15. Bardin N, Reumaux D, Geboes K, Colombel JF, Blot-Chabaud M, Sampol J, Duthilleul P, Dignat-George F (2006) Increased expression of CD146, a new marker of the endothelial junction in active inflammatory bowel disease. Inflamm Bowel Dis 12:16–21

    Article  PubMed  Google Scholar 

  16. Figarella-Branger D, Schleinitz N, Boutière-Albanèse B, Camoin L, Bardin N, Guis S, Pouget J, Cognet C, Pellissier JF, Dignat-George F (2006) Platelet-endothelial cell adhesion molecule-1 and CD146: soluble levels and in situ expression of cellular adhesion molecules implicated in the cohesion of endothelial cells in idiopathic inflammatory myopathies. J Rheumatol 33:1623–1630

    PubMed  CAS  Google Scholar 

  17. Spallarossa P, Garibaldi S, Barisione C, Ghigliotti G, Altieri P, Tracchi I, Fabbi P, Barsotti A, Brunelli C (2008) Postprandial serum induces apoptosis in endothelial cells: Role of polymorphonuclear-derived myeloperoxidase and metalloproteinase-9 activity. Atherosclerosis 198:458–467

    Article  PubMed  CAS  Google Scholar 

  18. Boneberg EM, Illges H, Legler DF, Fürstenberger G (2009) Soluble CD146 is generated by ectodomain shedding of membrane CD146 in a calcium-induced, matrix metalloprotease-dependent process. Microvasc Res 78:325–331

    Article  PubMed  CAS  Google Scholar 

  19. Bardin N, Blot-Chabaud M, Despoix N, Kebir A, Harhouri K, Arsanto JP, Spinosa L, Perrin P, Robert S, Vely F, Sabatier F, Lebivic A, Kaplanski G, Sampol J, Dignat-George F (2009) CD146 and its soluble form regulate monocyte transendothelial migration. Arterioscler Thromb Vasc Biol 29:746–753

    Article  PubMed  CAS  Google Scholar 

  20. Mobley JL, Leininger M, Madore S, Baginski TJ, Renkiewicz R (2007) Genetic evidence of a functional monocyte dichotomy. Inflammation 30:189–197

    Article  PubMed  Google Scholar 

  21. Skrzeczyńska-Moncznik J, Bzowska M, Loseke S, Grage-Griebenow E, Zembala M, Pryjma J (2008) Peripheral blood CD14high CD16+ monocytes are main producers of IL-10. Scand J Immunol 67:152–159

    Article  PubMed  Google Scholar 

  22. Ancuta P, Rao R, Moses A, Mehle A, Shaw SK, Luscinskas FW, Gabuzda D (2003) Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J Exp Med 197:1701–1707

    Article  PubMed  CAS  Google Scholar 

  23. Ancuta P, Moses A, Gabuzda D (2004) Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions. Immunobiology 209:11–20

    Article  PubMed  CAS  Google Scholar 

  24. 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

    Article  PubMed  CAS  Google Scholar 

  25. Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82

    Article  PubMed  CAS  Google Scholar 

  26. Barisione C, Garibaldi S, Ghigliotti G, Fabbi P, Altieri P, Casale MC, Spallarossa P, Bertero G, Balbi M, Corsiglia L, Brunelli C (2010) CD14CD16 monocyte subset levels in heart failure patients. Dis Markers 28:115–124

    PubMed  CAS  Google Scholar 

  27. Ross R (1999) Atherosclerosis–an inflammatory disease. N Engl J Med 340:115–126

    Article  PubMed  CAS  Google Scholar 

  28. Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, Llodra J, Garin A, Liu J, Mack M, van Rooijen N, Lira SA, Habenicht AJ, Randolph GJ (2007) Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 117:185–194

    Article  PubMed  CAS  Google Scholar 

  29. Ancuta P, Wang J, Gabuzda D (2006) CD16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells. J Leukoc Biol 80:1156–1164

    Article  PubMed  CAS  Google Scholar 

  30. 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

    Article  PubMed  CAS  Google Scholar 

  31. Shantsila E, Lip GY (2009) Monocyte diversity in myocardial infarction. J Am Coll Cardiol 54:139–142

    Article  PubMed  Google Scholar 

  32. Czepluch FS, Olieslagers S, van Hulten R, Vöö SA, Waltenberger J (2011) VEGF-A-induced chemotaxis of CD16+ monocytes is decreased secondary to lower VEGFR-1 expression. Atherosclerosis 215:331–338

    Article  PubMed  CAS  Google Scholar 

  33. Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B, Puel A, Biswas SK, Moshous D, Picard C, Jais JP, D’Cruz D, Casanova JL, Trouillet C, Geissmann F (2010) Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 33:375–386

    Article  PubMed  CAS  Google Scholar 

  34. Zawada AM, Rogacev KS, Rotter B, Winter P, Marell RR, Fliser D, Heine GH (2011) SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset. Blood 118:e50–e61

    Article  PubMed  CAS  Google Scholar 

  35. Wong KL, Tai JJ, Wong WC, Han H, Sem X, Yeap WH, Kourilsky P, Wong SC (2011) Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood 118:16–31

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Cardiology, Research Center of Cardiovascular Biology, University of Genova, Viale Benedetto XV, 6, 16132, Genova, Italy

    Silvano Garibaldi, Chiara Barisione, Giorgio Ghigliotti, Paolo Spallarossa, Antonio Barsotti, Patrizia Fabbi & Claudio Brunelli

  2. Casa Di Cura Istituto Cardiovascolare Camogli (ISC), Camogli, Italy

    Luca Corsiglia

  3. Unit of Vascular and Endovascular Surgery, University of Genova, Genova, Italy

    Daniela Palmieri & Domenico Palombo

Authors
  1. Silvano Garibaldi
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  2. Chiara Barisione
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  3. Giorgio Ghigliotti
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  4. Paolo Spallarossa
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  5. Antonio Barsotti
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  6. Patrizia Fabbi
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  7. Luca Corsiglia
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  8. Daniela Palmieri
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  9. Domenico Palombo
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  10. Claudio Brunelli
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Corresponding author

Correspondence to Silvano Garibaldi.

Additional information

Silvano Garibaldi and Chiara Barisione have contributed equally to this study.

Electronic supplementary material

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11033_2012_1499_MOESM1_ESM.jpg

Chart of correlation and correlation trend line between surface expression of CD146 and percentage of CD14++/CD16+ monocytes (JPEG 121 kb)

11033_2012_1499_MOESM2_ESM.jpg

Chart of correlation and correlation trend line between plasma soluble CD146 and percentage of CD14+/CD16+ monocytes (JPEG 99 kb)

11033_2012_1499_MOESM3_ESM.jpg

Chart of correlation and correlation trend line plasma soluble CD146 and percentage of CD146 positive monocytes relative to the CD14+/CD16+ subset (JPEG 104 kb)

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Garibaldi, S., Barisione, C., Ghigliotti, G. et al. Soluble form of the endothelial adhesion molecule CD146 binds preferentially CD16+ monocytes. Mol Biol Rep 39, 6745–6752 (2012). https://doi.org/10.1007/s11033-012-1499-x

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  • DOI: https://doi.org/10.1007/s11033-012-1499-x

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