C-reactive protein (CRP) induces chemokine secretion via CD11b/ICAM-1 interaction in human adherent monocytes
C-reactive protein (CRP) induces chemokine secretion via CD11b/ICAM-1 interaction in human adherent monocytes
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DOI：
10.1189/jlb.0208123
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发表时间：
2008-10-01
影响因子：
5.5
通讯作者：
Mach, Francois
中科院分区：
文献类型：
--
作者：
Montecucco, Fabrizio;Steffens, Sabine;Mach, Francois
一些研究支持C-反应蛋白（CRP）作为全身性心血管危险因素。最近在动脉内膜中检测到的CRP表明动脉粥样硬化中作为血管和免疫细胞的循环和组织介质的双重活性。在本论文中，我们专注于CRP对人单核细胞的炎症效应，这是由Ficoll-Percoll梯度分离和培养粘附聚苯乙烯，内皮细胞单层，或悬浮液中。采用ELISA、流式细胞术和实时荧光定量RT-PCR检测趋化因子水平、粘附分子和趋化因子受体表达。在Boy-den室中进行迁移测定。CRP刺激通过与CD 32a、CD 32 b和CD 64结合诱导贴壁单核细胞释放CCL 2、CCL 3和CCL 4，而在悬浮培养中未观察到影响。这与CRP诱导的粘附分子膜激活复合物1（Mac-1）和粘附单核细胞上的ICAM-1的上调有关。阻断Mac-1/ICAM-1相互作用可抑制CRP诱导的趋化因子分泌。此外，CRP降低粘附单核细胞中相应趋化因子受体CCR 1、CCR 2和CCR 5的mRNA和表面表达。这种效应是趋化因子分泌的结果，因为与中和性抗CCL 2、抗CCL 3和抗CCL 4抗体共孵育逆转了CRP的效应。因此，观察到CRP处理的单核细胞向CCL 2和CCL 3的迁移减少。总之，我们的数据表明，在体外模型，研究CRP的活动在粘附和悬浮的人单核细胞。CRP介导的粘附分子诱导和粘附单核细胞上趋化因子受体的减少可能有助于单核细胞在动脉粥样硬化病变内的滞留和其他循环细胞的募集。
Several studies support C-reactive protein (CRP) as a systemic cardiovascular risk factor. The recent detection of CRP in arterial intima suggests a dual activity in atherosclerosis as a circulating and tissue mediator on vascular and immune cells. In the present paper, we focused on the inflammatory effects of CRP on human monocytes, which were isolated by Ficoll-Percoll gradients and cultured in adherence to polystyrene, endothelial cell monolayer, or in suspension. Chemokine levels, adhesion molecule, and chemokine receptor expression were detected by ELISA, flow cytometry, and real-time RT-PCR. Migration assays were performed in a Boy-den chamber. Stimulation with CRP induced release of CCL2, CCL3, and CCL4 in adherent monocytes through the binding to CD32a, CD32b, and CD64, whereas no effect was observed in suspension culture. This was associated with CRP-induced up-regulation of adhesion molecules membrane-activated complex 1 (Mac-1) and ICAM-1 on adherent monocytes. Blockade of Mac-1/ICAM-1 interaction inhibited the CRP-induced chemokine secretion. In addition, CRP reduced mRNA and surface expression of corresponding chemokine receptors CCR1, CCR2, and CCR5 in adherent monocytes. This effect was a result of chemokine secretion, as coincubation with neutralizing anti-CCL2, anti-CCL3, and anti-CCL4 antibodies reversed the effect of CRP. Accordingly, a reduced migration of CRP-treated monocytes to CCL2 and CCL3 was observed. In conclusion, our data suggest an in vitro model to study CRP activities in adherent and suspension human monocytes. CRP-mediated induction of adhesion molecules and a decrease of chemokine receptors on adherent monocytes might contribute to the retention of monocytes within atherosclerotic lesions and recruitment of other circulating cells.