title: CD14 directs adventitial macrophage precursor recruitment: role in early abdominal aortic aneurysm formation.
abstract: BACKGROUND
  Recruitment of macrophage precursors to the adventitia plays a key role in the pathogenesis of abdominal aortic aneurysms (AAAs), but molecular mechanisms remain undefined. The innate immune signaling molecule CD14 was reported to be upregulated in adventitial macrophages in a murine model of AAA and in monocytes cocultured with aortic adventitial fibroblasts (AoAf) in vitro, concurrent with increased interleukin-6 (IL-6) expression. We hypothesized that CD14 plays a crucial role in adventitial macrophage precursor recruitment early during AAA formation.
  
  
  RESULTS
  CD14(-/-) mice were resistant to AAA formation induced by 2 different AAA induction models: aortic elastase infusion and systemic angiotensin II (AngII) infusion. CD14 gene deletion led to reduced aortic macrophage infiltration and diminished elastin degradation. Adventitial monocyte binding to AngII-infused aorta in vitro was dependent on CD14, and incubation of human acute monocytic leukemia cell line-1 (THP-1) monocytes with IL-6 or conditioned medium from perivascular adipose tissue (PVAT) upregulated CD14 expression. Conditioned medium from AoAf and PVAT induced CD14-dependent monocyte chemotaxis, which was potentiated by IL-6. CD14 expression in aorta and plasma CD14 levels were increased in AAA patients compared with controls.
  
  
  CONCLUSIONS
  These findings link CD14 innate immune signaling via a novel IL-6 amplification loop to adventitial macrophage precursor recruitment in the pathogenesis of AAA.
authors.affiliation: Division of Cardiovascular Diseases, University of Cincinnati, College of Medicine, Cincinnati, OH 45267-0769, USA. andra.blomkalns@uc.edu
authors.forename: Andra L
authors.initials: AL
authors.lastname: Blomkalns
authors.forename: Daniel
authors.initials: D
authors.lastname: Gavrila
authors.forename: Manesh
authors.initials: M
authors.lastname: Thomas
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Neltner
authors.forename: Victor M
authors.initials: VM
authors.lastname: Blanco
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Benjamin
authors.forename: Michael L
authors.initials: ML
authors.lastname: McCormick
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Stoll
authors.forename: Gerene M
authors.initials: GM
authors.lastname: Denning
authors.forename: Sean P
authors.initials: SP
authors.lastname: Collins
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Qin
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
authors.forename: Robert W
authors.initials: RW
authors.lastname: Thompson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Weiss
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lindower
authors.forename: Susan M
authors.initials: SM
authors.lastname: Pinney
authors.forename: Tapan
authors.initials: T
authors.lastname: Chatterjee
authors.forename: Neal L
authors.initials: NL
authors.lastname: Weintraub
mesh_terms: D063194:Adventitia / Q000276:immunology; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology*; D045744:Cell Line, Tumor; D054442:Cell Migration Assays, Macrophage; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D017737:Macrophages, Peritoneal; D051379:Mice; D008822:Mice, Transgenic; D055017:Monocyte-Macrophage Precursor Cells / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors
references.citation: Circ Res. 2009 Feb 27;104(4):541-9
references.pmid: 19122178
references.citation: Curr Opin Lipidol. 2006 Oct;17(5):527-33
references.pmid: 16960501
references.citation: J Occup Environ Med. 2009 Dec;51(12):1374-83
references.pmid: 19952785
references.citation: Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2576-81
references.pmid: 17962626
references.citation: Heart. 2004 Sep;90(9):983-8
references.pmid: 15310678
references.citation: Nat Med. 2005 Jun;11(6):653-60
references.pmid: 15880118
references.citation: Annu Rev Immunol. 2002;20:197-216
references.pmid: 11861602
references.citation: Circulation. 2001 Aug 21;104(8):914-20
references.pmid: 11514379
references.citation: Eur J Clin Invest. 2000 Feb;30(2):167-79
references.pmid: 10651843
references.citation: Gene. 2012 Apr 25;498(1):91-5
references.pmid: 22366371
references.citation: J Clin Invest. 2005 Nov;115(11):3149-56
references.pmid: 16211093
references.citation: Circulation. 2004 Feb 17;109(6):784-9
references.pmid: 14970116
references.citation: Circulation. 2001 Dec 18;104(25):3103-8
references.pmid: 11748108
references.citation: Immunity. 1996 Apr;4(4):407-14
references.pmid: 8612135
references.citation: Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1576-82
references.pmid: 12816876
references.citation: J Biol Chem. 2003 Aug 29;278(35):32921-8
references.pmid: 12816958
references.citation: Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1671-7
references.pmid: 15933246
references.citation: Cytometry A. 2008 Oct;73(10):926-30
references.pmid: 18752282
references.citation: Int J Occup Med Environ Health. 2003;16(2):139-53
references.pmid: 12921382
references.citation: J Clin Invest. 2009 Dec;119(12):3637-51
references.pmid: 19920349
references.citation: Immunology. 2004 Aug;112(4):521-30
references.pmid: 15270722
references.citation: J Vasc Res. 2011;48(3):261-72
references.pmid: 21099231
references.citation: J Vasc Surg. 2008 Oct;48(4):808-14
references.pmid: 18639426
references.citation: Circulation. 2006 Mar 21;113(11):e463-654
references.pmid: 16549646
references.citation: Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):429-34
references.pmid: 14739119
references.citation: Nat Immunol. 2005 Jun;6(6):565-70
references.pmid: 15895089
references.citation: J Biol Chem. 2002 Dec 6;277(49):47834-43
references.pmid: 12324469
references.citation: Eur J Vasc Endovasc Surg. 2004 Jan;27(1):65-74
references.pmid: 14652840
references.citation: Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):439-41
references.pmid: 17301319
references.citation: FEBS Lett. 2002 May 22;519(1-3):23-9
references.pmid: 12023012
references.citation: Br J Pharmacol. 2001 Oct;134(4):865-70
references.pmid: 11606327
references.citation: Immunity. 1994 Sep;1(6):509-16
references.pmid: 7534618
references.citation: Circulation. 2013 Jan 1;127(1):e6-e245
references.pmid: 23239837
references.citation: Ann N Y Acad Sci. 1996 Nov 18;800:157-74
references.pmid: 8958991
references.citation: Circulation. 2001 Feb 27;103(8):1064-70
references.pmid: 11222467
references.citation: Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2813-9
references.pmid: 21960563
references.citation: Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):461-9
references.pmid: 17218601
references.citation: Curr Opin Lipidol. 2002 Oct;13(5):513-21
references.pmid: 12352015
references.citation: Arterioscler Thromb Vasc Biol. 2002 Apr 1;22(4):560-5
references.pmid: 11950691
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: Nat Med. 2004 Apr;10(4):416-21
references.pmid: 15034566
references.citation: Immunol Rev. 2007 Oct;219:187-203
references.pmid: 17850490
references.citation: J Periodontal Res. 2011 Apr;46(2):176-83
references.pmid: 21143481
references.citation: Immunol Cell Biol. 2005 Oct;83(5):462-7
references.pmid: 16174094
references.citation: J Vasc Surg. 2010 Jun;51(6):1479-87
references.pmid: 20488324
references.citation: J Hypertens. 2003 Oct;21(10):1869-77
references.pmid: 14508193
references.citation: Infect Immun. 2009 Feb;77(2):725-32
references.pmid: 19047409
references.citation: Circulation. 2002 Mar 5;105(9):1135-43
references.pmid: 11877368
references.citation: J Immunol. 2004 Jul 15;173(2):1336-43
references.pmid: 15240728
references.citation: Circulation. 2002 Mar 12;105(10):1158-61
references.pmid: 11889007
references.citation: Infect Immun. 1998 Jan;66(1):28-35
references.pmid: 9423835