Title: CD14 directs adventitial macrophage precursor recruitment: role in early abdominal aortic aneurysm formation.
Authors: 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
Published In J Am Heart Assoc, (2013 Mar 08)
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.
PubMed ID: 23537804
MeSH Terms: Adventitia/immunology; Animals; Aortic Aneurysm, Abdominal/immunology*; Cell Line, Tumor; Cell Migration Assays, Macrophage; Cell Movement/immunology*; Cells, Cultured; Disease Models, Animal; Humans; Immunity, Innate; Interleukin-6/immunology*; Lipopolysaccharide Receptors/immunology*; Macrophages, Peritoneal; Macrophages/immunology*; Mice; Mice, Transgenic; Monocyte-Macrophage Precursor Cells/immunology*; Signal Transduction/immunology