C-Reactive Protein Elicits White Blood Cell Activation in Humans
C-Reactive Protein Elicits White Blood Cell Activation in Humans
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DOI：
10.1016/j.amjmed.2008.11.032
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发表时间：
2009-06-01
影响因子：
5.9
通讯作者：
Stroes, Erik S. G.
中科院分区：
文献类型：
--
作者：
Bisoendial, Radjesh J.;Birjmohun, Rakesh S.;Stroes, Erik S. G.
目的：一致的流行病学证据表明，急性感染增加急性心血管事件的风险。我们在人体中测试了重组人C-反应蛋白（rhCRP）给药后外周血白细胞的活化是否可能为感染性疾病促进动脉粥样硬化疾病提供一种机制。通过使用定量实时聚合酶链反应分析，在5名男性志愿者中，在输注1.25 mg/kg rhCRP之前和之后，分析95种炎性标志物的全血表达谱。在基线和rhCRP输注后4小时和8小时测量相关转录水平。CRP引起外周血白细胞中基质金属蛋白酶（MMP）-9、单核细胞趋化蛋白（MCP）-1、纤溶酶原激活物尿激酶、巨噬细胞炎性蛋白1 α和核因子κ B抑制剂mRNA的显著上调。MMP- 9和MCP-1的mRNA上调分别为17倍和11倍。MMP- 9（78 +/- 32 ng/mL至109 +/- 41 ng/mL; P = 0.014）和MCP-1（312 +/- 92 pg/mL至2590 +/- 898 pg/mL; P = 0.007）血浆蛋白水平的相应增加与mRNA结果密切相关。此外，在全血培养刺激试验中，CRP诱导促炎性变化。值得注意的是，热灭活废除了CRP的能力，引起这些促炎性变化，不包括纯化的CRP preparation.CONCLUSION内的污染物的作用：CRP elaborate激活外周血白细胞，随后分泌斑块不稳定介质。这些发现与感染性疾病触发动脉粥样硬化表现的假设一致，其中CRP升高可能有助于心血管事件的发生。(C)2009 Elsevier Inc. All rights reserved.美国医学杂志（2009）122，582。e1-582.e9
OBJECTIVE: Consistent epidemiologic evidence suggests that acute infections increase the risk for acute cardiovascular events. We tested in humans whether activation of peripheral leukocytes in reaction to the administration of recombinant human C-reactive protein (rhCRP) may provide a mechanism for infectious diseases to promote atherosclerotic disease.METHODS AND RESULTS: By using quantitative real-time polymerase chain reaction analysis, whole-blood expression profiles were analyzed for 95 inflammatory markers before and after infusion of 1.25 mg/kg rhCRP in 5 male volunteers. Relevant transcript levels were measured at baseline and 4 and 8 hours after rhCRP-infusion. CRP caused significant up-regulation of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, plasminogen activator urokinase, macrophage inflammatory protein 1 alpha, and nuclear factor of kappa B inhibitor mRNAs in peripheral leukocytes. mRNA up-regulation of MMP- 9 and MCP-1 was 17- and 11-fold, respectively. The corresponding increase in plasma protein levels of MMP- 9 (78 +/- 32 ng/mL to 109 +/- 41 ng/mL; P = .014) and MCP-1 (312 +/- 92 pg/mL to 2590 +/- 898 pg/mL; P = .007) closely mirrored mRNA findings. Also, in whole-blood culture stimulation assays, CRP induced proinflammatory changes. Notably, heat inactivation abolished the capacity of CRP to evoke these proinflammatory changes, excluding a role for contaminants within the purified CRP preparation.CONCLUSION: CRP elicits activation of peripheral leukocytes with ensuing secretion of plaque-destabilizing mediators. These findings are consistent with the hypothesis that infectious diseases trigger manifestations of atherosclerosis, in which CRP elevation might contribute to the onset of cardiovascular events. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 582. e1-582.e9