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

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.