Induced macrophage activation in live excised atherosclerotic plaque

被引:20
作者
Prebble, Hannah [1 ]
Cross, Sean [1 ]
Marks, Edward [1 ]
Healy, Joe [1 ]
Searle, Emily [2 ]
Aamir, Raja [3 ]
Butler, Anthony [2 ,3 ]
Roake, Justin [4 ]
Hock, Barry [5 ]
Anderson, Nigel [3 ]
Gieseg, Steven P. [1 ,3 ]
机构
[1] Univ Canterbury, Sch Biol Sci, Free Rad Biochem Lab, Private Bag 4800, Christchurch, New Zealand
[2] Univ Canterbury, Sch Phys & Astron, Private Bag 4800, Christchurch, New Zealand
[3] Univ Otago Christchurch, Dept Radiol, POB 4345, Christchurch, New Zealand
[4] Christchurch Hosp, Dept Vasc Surg, Private Bag 4710, Christchurch, New Zealand
[5] Christchurch Hosp, Dept Pathol, Hematol Res Grp, Private Bag 4710, Christchurch, New Zealand
关键词
Carotid plaque; Macrophage; Neopterin; Inflammation; Spectral X-ray-imaging; GTP CYCLOHYDROLASE-I; INFLAMMATORY BIOMARKERS; PROGNOSTIC VALUE; SERUM NEOPTERIN; IMMUNE-RESPONSE; CELLS; 7,8-DIHYDRONEOPTERIN; DESTABILIZATION; PROGRESSION; MODULATION;
D O I
10.1016/j.imbio.2018.03.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Atherosclerotic plaques are complex tissues containing many different cell types. Macrophages contribute to inflammation, formation of the necrotic core, and plaque rupture. We examined whether macrophages in plaque can be activated and compared this to monolayer cells. The volume of calcium in the plaque was compared to the level of macrophage activation measured by total neopterin output. Carotid plaque samples were cut into 3 mm sections and cultured for up to 96 h. Live sections were stimulated with interferon-gamma, phytohaemagglutinin or phorbol 12-myristate 13-acetate. Macrophage activation and oxidative stress were monitored by total neopterin (oxidized and non-oxidized 7, 8-dihydroneopterin) and neopterin levels every 24 h for up to 4 d. The calcium content of two plaques was investigated by spectral imaging. Direct stimulation of macrophages in plaque sections with interferon-gamma caused a sustained increase in neopterin (p = .037) and total neopterin (p = .003). The addition of phorbol 12-myristate 13-acetate to plaque had no significant effect on total neopterin production (p = .073) but increased neopterin (p = .037) whereas phytohaemagglutinin caused a significant increase in both neopterin and total neopterin (p = .0279 and .0168). There was an inverse association (R-2 = 0.91) between the volume of calcium and macrophage activation as measured by total neopterin production in stimulated plaque tissue. Resident macrophages within excised carotid plaque activated either directly or indirectly generate the biomarkers 7,8-dihydroneopterin and neopterin. Macrophage activation rather than the oxidative environment is associated with plaque calcification.
引用
收藏
页码:526 / 535
页数:10
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