CD14 directs adventitial macrophage precursor recruitment: role in early abdominal aortic aneurysm formation.

Andra L. Blomkalns, Daniel Gavrila, Manesh Thomas, Bonnie S. Neltner, Victor M. Blanco, Stephanie B. Benjamin, Michael L. McCormick, Lynn L. Stoll, Gerene M. Denning, Sean P. Collins, Zhenyu Qin, Alan Daugherty, Lisa A. Cassis, Robert W. Thompson, Robert M. Weiss, Paul D. Lindower, Susan M. Pinney, Tapan Kumar Chatterjee, Neal Lee Weintraub

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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. 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. These findings link CD14 innate immune signaling via a novel IL-6 amplification loop to adventitial macrophage precursor recruitment in the pathogenesis of AAA.

Original languageEnglish (US)
Pages (from-to)e000065
JournalUnknown Journal
Volume2
Issue number2
DOIs
StatePublished - Apr 2013

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Adventitia
Abdominal Aortic Aneurysm
Macrophages
Monocytes
Interleukin-6
Conditioned Culture Medium
Angiotensin II
Aorta
Adipose Tissue
Fibroblasts
Leukemia, Monocytic, Acute
Elastin
Pancreatic Elastase
Gene Deletion
Chemotaxis
Cell Line

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

CD14 directs adventitial macrophage precursor recruitment : role in early abdominal aortic aneurysm formation. / Blomkalns, Andra L.; Gavrila, Daniel; Thomas, Manesh; Neltner, Bonnie S.; Blanco, Victor M.; Benjamin, Stephanie B.; McCormick, Michael L.; Stoll, Lynn L.; Denning, Gerene M.; Collins, Sean P.; Qin, Zhenyu; Daugherty, Alan; Cassis, Lisa A.; Thompson, Robert W.; Weiss, Robert M.; Lindower, Paul D.; Pinney, Susan M.; Chatterjee, Tapan Kumar; Weintraub, Neal Lee.

In: Unknown Journal, Vol. 2, No. 2, 04.2013, p. e000065.

Research output: Contribution to journalArticle

Blomkalns, AL, Gavrila, D, Thomas, M, Neltner, BS, Blanco, VM, Benjamin, SB, McCormick, ML, Stoll, LL, Denning, GM, Collins, SP, Qin, Z, Daugherty, A, Cassis, LA, Thompson, RW, Weiss, RM, Lindower, PD, Pinney, SM, Chatterjee, TK & Weintraub, NL 2013, 'CD14 directs adventitial macrophage precursor recruitment: role in early abdominal aortic aneurysm formation.', Unknown Journal, vol. 2, no. 2, pp. e000065. https://doi.org/10.1161/JAHA.112.000065
Blomkalns, Andra L. ; Gavrila, Daniel ; Thomas, Manesh ; Neltner, Bonnie S. ; Blanco, Victor M. ; Benjamin, Stephanie B. ; McCormick, Michael L. ; Stoll, Lynn L. ; Denning, Gerene M. ; Collins, Sean P. ; Qin, Zhenyu ; Daugherty, Alan ; Cassis, Lisa A. ; Thompson, Robert W. ; Weiss, Robert M. ; Lindower, Paul D. ; Pinney, Susan M. ; Chatterjee, Tapan Kumar ; Weintraub, Neal Lee. / CD14 directs adventitial macrophage precursor recruitment : role in early abdominal aortic aneurysm formation. In: Unknown Journal. 2013 ; Vol. 2, No. 2. pp. e000065.
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