Open AccessCD 14 Directs Adventitial Macrophage Precursor Recruitment: Role in Early Abdominal Aortic Aneurysm Formation
Author(s) -
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,
Weintraub Neal L.
Publication year - 2013
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.112.000065
Subject(s) - cd14 , medicine , monocyte , macrophage , adventitia , innate immune system , elastin , angiotensin ii , microbiology and biotechnology , inflammation , cancer research , immunology , immune system , in vitro , biology , pathology , receptor , biochemistry
Background Recruitment of macrophage precursors to the adventitia plays a key role in the pathogenesis of abdominal aortic aneurysms ( AAA s), but molecular mechanisms remain undefined. The innate immune signaling molecule CD 14 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 CD 14 plays a crucial role in adventitial macrophage precursor recruitment early during AAA formation. Methods and Results CD 14 −/− mice were resistant to AAA formation induced by 2 different AAA induction models: aortic elastase infusion and systemic angiotensin II (Ang II ) infusion. CD 14 gene deletion led to reduced aortic macrophage infiltration and diminished elastin degradation. Adventitial monocyte binding to Ang II ‐infused aorta in vitro was dependent on CD 14, 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 CD 14 expression. Conditioned medium from AoAf and PVAT induced CD 14‐dependent monocyte chemotaxis, which was potentiated by IL ‐6. CD 14 expression in aorta and plasma CD 14 levels were increased in AAA patients compared with controls. Conclusions These findings link CD 14 innate immune signaling via a novel IL ‐6 amplification loop to adventitial macrophage precursor recruitment in the pathogenesis of AAA .