title: Polymorphonuclear neutrophils and instability of the atherosclerotic plaque: a causative role?
abstract: OBJECTIVE
  The aim of this review is to examine the role of polymorphonuclear neutrophils (PMNs) in the evolution of atherosclerosis.
  
  
  BACKGROUND
  While the role of PMNs in the evolution of atherosclerosic process has failed until recently to attract much attention, a body of research carried out over the last decade has disclosed the unexpectedly complex behavior of these cells, unraveling an unexpected key role for PMNs in the onset and progression of atheroma.
  
  
  METHODS
  A PubMed database search was performed for studies providing evidences on the role of PMNs in the development and progression of atherosclerotic lesion.
  
  
  CONCLUSIONS
  Activated PMNs were shown to produce and release reactive oxygen species, inflammatory leukotrienes and proteolytic lysosomal enzymes, directly inducing vascular damage. Activated PMNs also secrete myeloperoxidase, involved in lipoprotein oxidation. PMNs have a finite lifespan and typically die through apoptosis, which thus represents a counter-regulatory mechanism limiting the toxic potential of these short-lived, terminally differentiated cells. Dysregulation of this process probably contributes to the pathogenesis and progression of several inflammatory diseases. Moreover, high circulating levels of PMN-platelet aggregates have been reported in patients with clinical atherosclerosis, and recent studies suggest that these aggregates may play a role in vascular response to injury. It has been suggested that this heterotypic interaction between platelets and leukocytes might represent a link between hemostasis/thrombosis and the inflammatory response.
authors.affiliation: Cardiovascular and Neurologic Department, Ospedale San Donato, Arezzo, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Della Bona
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cardillo
authors.forename: Milena
authors.initials: M
authors.lastname: Leo
authors.forename: Gina
authors.initials: G
authors.lastname: Biasillo
authors.forename: Massimo
authors.initials: M
authors.lastname: Gustapane
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Biasucci
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology*; D006801:Humans; D009504:Neutrophils / Q000276:immunology*; D009195:Peroxidase / Q000276:immunology; D058226:Plaque, Atherosclerotic / Q000276:immunology*
chemical_list: D009195:Peroxidase
references.citation: J Exp Med. 2009 Aug 31;206(9):1983-94
references.pmid: 19703986
references.citation: Cell. 1989 Oct 20;59(2):305-12
references.pmid: 2478294
references.citation: J Leukoc Biol. 2000 Jul;68(1):9-14
references.pmid: 10914484
references.citation: Antioxid Redox Signal. 2012 Dec 15;17(12):1785-95
references.pmid: 22540532
references.citation: J Immunol. 1997 Apr 1;158(7):3372-7
references.pmid: 9120296
references.citation: Am J Pathol. 2001 Mar;158(3):879-91
references.pmid: 11238037
references.citation: Nature. 2007 Oct 4;449(7162):564-9
references.pmid: 17873860
references.citation: J Biol Chem. 2000 Dec 1;275(48):37524-32
references.pmid: 11090610
references.citation: Blood. 2002 Mar 1;99(5):1802-10
references.pmid: 11861298
references.citation: Blood. 2009 May 21;113(21):5254-65
references.pmid: 19264679
references.citation: Circulation. 2010 Nov 2;122(18):1837-45
references.pmid: 20956207
references.citation: Physiol Rev. 2006 Apr;86(2):515-81
references.pmid: 16601268
references.citation: Clin Immunol. 2008 Apr;127(1):89-97
references.pmid: 18294918
references.citation: Circulation. 2006 Apr 18;113(15):1871-8
references.pmid: 16606792
references.citation: Arterioscler Thromb Vasc Biol. 1999 Feb;19(2):372-7
references.pmid: 9974421
references.citation: Nucleic Acids Res. 2006 May 08;34(8):2408-17
references.pmid: 16682448
references.citation: J Am Coll Cardiol. 2007 May 22;49(20):1993-2000
references.pmid: 17512353
references.citation: J Biol Chem. 1999 Sep 10;274(37):26141-8
references.pmid: 10473565
references.citation: Ann Epidemiol. 2005 Apr;15(4):266-71
references.pmid: 15780773
references.citation: Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):84-9
references.pmid: 17991873
references.citation: J Clin Invest. 1997 May 1;99(9):2075-81
references.pmid: 9151778
references.citation: Science. 2002 Jun 28;296(5577):2391-4
references.pmid: 12089442
references.citation: J Exp Med. 2000 Jan 3;191(1):189-94
references.pmid: 10620617
references.citation: Circulation. 2008 Jun 24;117(25):3168-70
references.pmid: 18574058
references.citation: Circ Res. 2008 Feb 1;102(2):209-17
references.pmid: 17991882
references.citation: Am J Physiol. 1994 Dec;267(6 Pt 1):L775-85
references.pmid: 7810682
references.citation: Circulation. 1999 Apr 6;99(13):1753-9
references.pmid: 10190887
references.citation: J Lipid Res. 2005 Jun;46(6):1081-92
references.pmid: 15834121
references.citation: Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2688-95
references.pmid: 17023679
references.citation: Nat Rev Immunol. 2008 Oct;8(10):802-15
references.pmid: 18825131
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8264-8
references.pmid: 7667279
references.citation: J Immunol. 1995 Oct 15;155(8):3711-5
references.pmid: 7561072
references.citation: J Clin Invest. 1996 Mar 15;97(6):1525-34
references.pmid: 8617886
references.citation: Circulation. 1999 Nov 23;100(21):2135-9
references.pmid: 10571971
references.citation: Circulation. 1989 Mar;79(3):549-56
references.pmid: 2537159
references.citation: Science. 1994 Dec 23;266(5193):2011-5
references.pmid: 7605428
references.citation: N Engl J Med. 2002 Jul 4;347(1):5-12
references.pmid: 12097534
references.citation: Immunol Rev. 2003 Jun;193:101-10
references.pmid: 12752675
references.citation: Circulation. 2006 Feb 7;113(5):640-6
references.pmid: 16461836
references.citation: Blood. 2011 Sep 22;118(12):3359-66
references.pmid: 21705500
references.citation: Curr Opin Immunol. 2002 Feb;14(1):123-8
references.pmid: 11790542
references.citation: PLoS One. 2012;7(6):e39484
references.pmid: 22761804
references.citation: Nat Med. 2002 Jan;8(1):61-7
references.pmid: 11786908
references.citation: J Leukoc Biol. 2000 May;67(5):662-8
references.pmid: 10811006
references.citation: Am J Hematol. 2008 Apr;83(4):288-95
references.pmid: 17924549
references.citation: Front Biosci. 2008 May 01;13:3760-7
references.pmid: 18508470
references.citation: Trends Immunol. 2007 Aug;28(8):340-5
references.pmid: 17627888
references.citation: Blood. 1996 Dec 1;88(11):4183-94
references.pmid: 8943853
references.citation: Circulation. 1996 Sep 15;94(6):1239-46
references.pmid: 8822975
references.citation: J Biol Chem. 2012 Oct 5;287(41):34101-9
references.pmid: 22879591
references.citation: Blood. 1985 Feb;65(2):484-91
references.pmid: 2981591
references.citation: Circulation. 2010 Dec 14;122(24):2505-13
references.pmid: 21126969
references.citation: Circulation. 1993 Aug;88(2):358-63
references.pmid: 8101771
references.citation: J Leukoc Biol. 2004 May;75(5):828-35
references.pmid: 14742636
references.citation: Trends Immunol. 2009 Nov;30(11):547-56
references.pmid: 19783480
references.citation: Blood. 1992 Oct 15;80(8):2012-20
references.pmid: 1382715
references.citation: Clin Immunol. 2007 Jul;124(1):90-7
references.pmid: 17512253
references.citation: Circulation. 1998 Sep 29;98(13):1322-8
references.pmid: 9751682
references.citation: J Exp Med. 2012 Apr 9;209(4):819-35
references.pmid: 22451716
references.citation: J Am Soc Nephrol. 2001 May;12(5):932-940
references.pmid: 11316851
references.citation: J Mol Med (Berl). 2006 Feb;84(2):122-5
references.pmid: 16362398
references.citation: Circ Res. 2006 May 12;98(9):1168-76
references.pmid: 16601227
references.citation: Heart. 2004 Aug;90(8):847-52
references.pmid: 15253949
references.citation: Zhonghua Xin Xue Guan Bing Za Zhi. 2007 Mar;35(3):241-4
references.pmid: 17582289
references.citation: Circulation. 2005 Nov 8;112(19):2993-3000
references.pmid: 16260637
references.citation: J Clin Invest. 1995 May;95(5):2297-303
references.pmid: 7537762
references.citation: Circulation. 2002 Dec 3;106(23):2894-900
references.pmid: 12460868
references.citation: Immunology. 2004 Feb;111(2):186-94
references.pmid: 15027904
references.citation: Annu Rev Immunol. 2002;20:197-216
references.pmid: 11861602
references.citation: Circulation. 2001 Sep 25;104(13):1533-7
references.pmid: 11571248
references.citation: J Immunol. 2005 May 15;174(10):6399-405
references.pmid: 15879141
references.citation: Eur Heart J. 2009 Sep;30(18):2220-5
references.pmid: 19556261
references.citation: Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2151-6
references.pmid: 16051881
references.citation: J Clin Invest. 1999 Jun;103(11):1547-60
references.pmid: 10359564
references.citation: Thromb Haemost. 2012 Mar;107(3):597-8
references.pmid: 22318427
references.citation: Cell. 1994 Jan 28;76(2):301-14
references.pmid: 7507411
references.citation: FASEB J. 2009 Jun;23(6):1750-7
references.pmid: 19151333
references.citation: N Engl J Med. 1974 Jun 6;290(23):1275-8
references.pmid: 4827627
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1143-6
references.pmid: 15237089
references.citation: Int Arch Allergy Immunol. 2001 Oct;126(2):147-56
references.pmid: 11729353
references.citation: J Surg Res. 2006 Jun 15;133(2):143-9
references.pmid: 16360172
references.citation: Nature. 2006 Jul 27;442(7101):457-60
references.pmid: 16871217
references.citation: Sci Transl Med. 2011 Oct 5;3(103):103ra98
references.pmid: 21974936
references.citation: J Am Soc Nephrol. 2004 Aug;15(8):1983-92
references.pmid: 15284284
references.citation: Atherosclerosis. 2004 Jul;175(1):151-7
references.pmid: 15186960
references.citation: J Am Coll Cardiol. 2007 Jul 10;50(2):159-65
references.pmid: 17616301
references.citation: Blood. 2009 Nov 19;114(21):4613-23
references.pmid: 19696199
references.citation: Blood. 2008 Aug 15;112(4):1461-71
references.pmid: 18490516
references.citation: Thromb Haemost. 2011 Nov;106(5):839-48
references.pmid: 22012406
references.citation: Circ Res. 2012 Mar 16;110(6):875-88
references.pmid: 22427325
references.citation: J Leukoc Biol. 2005 Dec;78(6):1408-18
references.pmid: 16204629
references.citation: Am J Cardiol. 2005 Feb 15;95(4):452-6
references.pmid: 15695127
references.citation: J Clin Invest. 2004 Aug;114(4):529-41
references.pmid: 15314690
references.citation: Semin Immunopathol. 2009 Jun;31(1):35-47
references.pmid: 19238385
references.citation: Arch Biochem Biophys. 2006 Jan 15;445(2):245-55
references.pmid: 16171772
references.citation: Circ Res. 2006 Nov 10;99(10):1100-8
references.pmid: 17038639
references.citation: Nat Rev Immunol. 2011 Jul 25;11(8):519-31
references.pmid: 21785456
references.citation: Cell. 2005 Mar 11;120(5):649-61
references.pmid: 15766528
references.citation: J Biol Chem. 2004 May 14;279(20):21085-95
references.pmid: 14766748
references.citation: Int Immunopharmacol. 2010 Nov;10(11):1325-34
references.pmid: 20828640
references.citation: Pharmacol Ther. 2006 Jul;111(1):16-26
references.pmid: 16476484
references.citation: Arterioscler Thromb Vasc Biol. 2006 Jun;26(6):1304-9
references.pmid: 16574894
references.citation: Am J Cardiol. 1996 Oct 15;78(8):945-8
references.pmid: 8888672
references.citation: N Engl J Med. 2005 Apr 21;352(16):1685-95
references.pmid: 15843671
references.citation: J Clin Invest. 1994 Jul;94(1):437-44
references.pmid: 8040285
references.citation: J Leukoc Biol. 2006 Sep;80(3):521-8
references.pmid: 16793915
references.citation: Circulation. 2000 Jun 27;101(25):2883-8
references.pmid: 10869258
references.citation: Trends Immunol. 2009 Nov;30(11):538-46
references.pmid: 19699683
references.citation: J Leukoc Biol. 2005 Jul;78(1):301-9
references.pmid: 15845643
references.citation: Biochem J. 2005 Oct 1;391(Pt 1):125-34
references.pmid: 15932347
references.citation: JAMA. 2001 Nov 7;286(17):2136-42
references.pmid: 11694155
references.citation: J Am Coll Cardiol. 1996 Mar 1;27(3):611-6
references.pmid: 8606272
references.citation: J Exp Med. 1997 Aug 29;186(5):739-47
references.pmid: 9271589
references.citation: Circulation. 2008 Oct 28;118(18):1837-47
references.pmid: 18852364
references.citation: J Biol Chem. 1976 Dec 25;251(24):7816-20
references.pmid: 826538
references.citation: Circulation. 2004 Mar 16;109(10):1230-5
references.pmid: 14993140
references.citation: J Biol Chem. 2001 Nov 2;276(44):41279-87
references.pmid: 11533038
references.citation: Blood. 1990 Feb 1;75(3):550-4
references.pmid: 1688717
references.citation: J Am Coll Cardiol. 2007 Dec 18;50(25):2369-74
references.pmid: 18154960
references.citation: Semin Hematol. 1994 Oct;31(4):261-9
references.pmid: 7831571
references.citation: Lancet. 2003 Sep 20;362(9388):983-8
references.pmid: 14511933
references.citation: Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1842-8
references.pmid: 20595650
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1102-11
references.pmid: 15790935
references.citation: Am J Pathol. 2010 Jul;177(1):493-500
references.pmid: 20472897
references.citation: Br J Haematol. 2000 May;109(2):272-9
references.pmid: 10848812
references.citation: Arterioscler Thromb Vasc Biol. 2003 Apr 1;23(4):535-42
references.pmid: 12615660
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1309-14
references.pmid: 15142860
references.citation: Blood. 1996 Jul 1;88(1):146-57
references.pmid: 8704169
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15880-5
references.pmid: 20798043
references.citation: Circulation. 2002 Feb 5;105(5):570-5
references.pmid: 11827921
references.citation: J Mol Cell Cardiol. 2012 May;52(5):962-70
references.pmid: 22266063
references.citation: J Pharmacol Exp Ther. 2006 Sep;318(3):1044-9
references.pmid: 16717106
references.citation: Circulation. 2012 Apr 3;125(13):1673-83
references.pmid: 22388324
references.citation: Annu Rev Pathol. 2008;3:279-312
references.pmid: 18233953
references.citation: Blood. 1964 Dec;24:780-803
references.pmid: 14235362
references.citation: Arch Surg. 1996 Jan;131(1):24-9; discussion 29-30
references.pmid: 8546573
references.citation: Arterioscler Thromb Vasc Biol. 1995 Aug;15(8):1121-30
references.pmid: 7627705