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Dendritic cell subset distributions in the aorta in healthy and atherosclerotic mice.

ABSTRACT: Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr (-/-)) mice, CD11c(+) MHCII(+) DCs could be discriminated into CD103(-) CD11b(+)F4/80(+), CD11b(+)F4/80(-) and CD11b(-)F4/80(-) DCs and CD103(+) CD11b(-)F4/80(-) DCs. Except for CD103(-) CD11b(-) F4/80(-) DCs, these subsets expanded in high fat diet-fed Ldlr (-/-) mice. Signal-regulatory protein (Sirp)-? was detected on aortic macrophages, CD11b(+) DCs, and partially on CD103(-) CD11b(-) F4/80(-) but not on CD103(+) DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l (-/-)) mice, a specific loss of CD103(+) DCs but also CD103(-) CD11b(+) F4/80(-) DCs was evidenced. Aortic CD103(+) and CD11b(+) F4/80(-) CD103(-) DCs may thus belong to conventional rather than monocyte-derived DCs, given their dependence on Flt3L-signalling. CD64, postulated to distinguish macrophages from DCs, could not be detected on DC subsets under physiological conditions, but appeared in a fraction of CD103(-) CD11b(+) F4/80(-) and CD11b(+) F4/80(+) cells in atherosclerotic Ldlr (-/-) mice. The emergence of CD64 expression in atherosclerosis may indicate that CD11b(+) F4/80(-) DCs similar to CD11b(+) F4/80(+) DCs are at least in part derived from immigrated monocytes during atherosclerotic lesion formation. Our data advance our knowledge about the presence of distinct DC subsets and their accumulation characteristics in atherosclerosis, and may help to assist in future studies aiming at specific DC-based therapeutic strategies for the treatment of chronic vascular inflammation.

SUBMITTER: Busch M

PROVIDER: S-EPMC3925240 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Dendritic cell subset distributions in the aorta in healthy and atherosclerotic mice.

Busch Martin M Westhofen Thilo C TC Koch Miriam M Lutz Manfred B MB Zernecke Alma A

PloS one 20140214 2

Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr (-/-)) ...[more]

PMID: 24551105

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Project description:Background Penetrating ulcers of aorta, aortic dissections and intramural hematomas all come under acute aortic syndromes and have important similarities and differences. Case report We report a 67?year old man with rupture of a large penetrating ulcer of the distal ascending aorta with hemopericardium and left hemothorax. He underwent interposition graft replacement of ascending aorta and hemi-arch with a 30?mm Gelweave Vascutek graft but represented 6?months later with development of a penetrating ulcer which ruptured into a huge 14?cm pseudoaneurysm. This was repaired with a 28?mm Vascutek Gelseal graft replacement of arch and interposition graft reconstruction of innominate and left common carotid arteries. 6?weeks later, however, he ruptured his proximal descending aorta and underwent TEVAR satisfactorily. Unfortunately, 2?days later, he developed a pathological fracture of left proximal tibia with metastasis from a primary renal cell carcinoma. He died 3?weeks later from respiratory failure. We shall briefly outline the similarities and differences in presentation and management of penetrating aortic ulcers, aortic dissections and intramural haematomas. We shall discuss, in greater detail, penetrating ulcers of thoracic aorta, their natural history, location, complications and management. Conclusion This case report is unique on account of initial successful surgical redressal following rupture of penetrating ulcer of distal ascending aorta into left pleural and pericardial cavities, normally associated with instant death. The haemodynamic effects of the rupture were staggered due to initial contained rupture into a smaller pseudoaneurysm, followed by a further rupture into a false aneurysmal sac followed eventually by generalised rupture into the pleural and pericardial cavities - a unique way of aortic rupture. Further development of another penetrating ulcer and a small pseudoaneurysm in the distal arch 6?months later which further ruptured into a larger 14?cm false aneurysmal sac, which again did not result in exsanguination, is again extraordinarily rare. Thereafter he underwent emergency thoracic endovascular aortic repair (TEVAR) for a further rupture of descending thoracic aorta. All three ruptures were managed successfully and would usually be associated with near-certain death, only for the patient to succumb eventually to the complications of metastatic renal cell carcinoma.

Dataset Information

Dendritic cell subset distributions in the aorta in healthy and atherosclerotic mice.

Publications

Dendritic cell subset distributions in the aorta in healthy and atherosclerotic mice.

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