Influence of chylomicron remnants on human monocyte activation in vitro.
Influence of chylomicron remnants on human monocyte activation in vitro.
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DOI：
10.1016/j.numecd.2010.02.019
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Lawson C
中科院分区：
文献类型：
--
作者：
Bentley C;Hathaway N;Widdows J;Bejta F;De Pascale C;Avella M;Wheeler-Jones CP;Botham KM;Lawson C
已知动脉粥样硬化是一种炎性疾病，并且越来越多的证据表明乳糜微粒残留物（CMR）（血液中携带膳食脂肪的脂蛋白）引起巨噬细胞泡沫细胞形成和炎症。在早期动脉粥样硬化中，外周循环中活化单核细胞的频率增加，血液中CMR的清除可能延迟，然而，CMR是否直接促进单核细胞活化并随后进入动脉壁尚未确定。在此，使用体外模型评估CMR对单核细胞促炎途径活化的贡献。原代人单核细胞和CMR样颗粒（CRLP）用于测量单核细胞活化的几个终点。CRLP治疗引起单核细胞快速和长期产生活性氧。促炎趋化因子MCP-1和IL-8在不存在CRLP的情况下由细胞以纳克量分泌。IL-8分泌在CRLP处理后短暂增加，并且在IL-8产生的药理学抑制剂存在下CRLP维持分泌。相反，暴露于CRLP显著降低MCP-1分泌。趋化性对MCP-1的增加，在单核细胞预先暴露于CRLP和逆转加入外源性MCP-1。我们的研究结果表明，CRLP激活人单核细胞，并增加其迁移在体外通过减少细胞MCP-1的表达。我们的数据支持目前的假设，CMR有助于动脉壁的炎症环境在早期动脉粥样硬化，并建议，这可能反映了与循环血单核细胞的直接相互作用。
Atherosclerosis is known to be an inflammatory disease and there is increasing evidence that chylomicron remnants (CMR), the lipoproteins which carry dietary fats in the blood, cause macrophage foam cell formation and inflammation. In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is increased, and clearance of CMR from blood may be delayed, however, whether CMR contribute directly to monocyte activation and subsequent egress into the arterial wall has not been established. Here, the contribution of CMR to activation of monocyte pro-inflammatory pathways was assessed using an in vitro model. Primary human monocytes and CMR-like particles (CRLP) were used to measure several endpoints of monocyte activation. Treatment with CRLP caused rapid and prolonged generation of reactive oxygen species by monocytes. The pro-inflammatory chemokines MCP-1 and IL-8 were secreted in nanogram quantities by the cells in the absence of CRLP. IL-8 secretion was transiently increased after CRLP treatment, and CRLP maintained secretion in the presence of pharmacological inhibitors of IL-8 production. In contrast, exposure to CRLP significantly reduced MCP-1 secretion. Chemotaxis towards MCP-1 was increased in monocytes pre-exposed to CRLP and was reversed by addition of exogenous MCP-1. Our findings indicate that CRLP activate human monocytes and augment their migration in vitro by reducing cellular MCP-1 expression. Our data support the current hypothesis that CMR contribute to the inflammatory milieu of the arterial wall in early atherosclerosis, and suggest that this may reflect direct interaction with circulating blood monocytes.
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影响因子：
7.1
作者：
Bellido, C;López-Miranda, J;Pérez-Jiménez, F
通讯作者：
Pérez-Jiménez, F
影响因子：
7.4
作者：
Barbieri, SS;Cavalca, V;Colli, S
通讯作者：
Colli, S
影响因子：
5.4
作者：
De Pascale, Clara;Avella, Michael;Botham, Kathleen M.
通讯作者：
Botham, Kathleen M.
DOI：
10.1161/01.atv.0000146267.71816.30
发表时间：
2004-12-01
影响因子：
8.7
作者：
Annuzzi, G;De Natale, C;Rivellese, AA
通讯作者：
Rivellese, AA
DOI：
10.1152/ajpheart.00432.2007
发表时间：
2007-10-01
影响因子：
4.8
作者：
Carluccio, Maria Annunziata;Ancora, Maria Assunta;De Caterina, Raffaele
通讯作者：
De Caterina, Raffaele