Endothelial microparticles (EMP) bind and activate monocytes: Elevated empmonocyte conjugates in multiple sclerosis
Endothelial microparticles (EMP) bind and activate monocytes: Elevated empmonocyte conjugates in multiple sclerosis
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DOI：
10.2741/1466
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发表时间：
2004-09-01
影响因子：
3.1
通讯作者：
Ahn, YS
中科院分区：
文献类型：
--
作者：
Jy, W;Minagar, A;Ahn, YS
据记录，MS 恶化期间血浆内皮微粒 (EMP) 升高。然而，EMP 在 MS 发病机制中的作用仍不清楚。我们研究了 EMP-单核细胞缀合物 (EMP-MoC) 的形成及其在 MS 炎症细胞跨内皮迁移中的潜在作用。对 30 名急性 MS 患者、20 名缓解期患者和 35 名对照患者进行了 EMP-MoC 检测。通过使用 α-CD54 或 α-CD62E 检测 EMP，使用 α-CD45 检测白细胞，以流式细胞术研究 EMP-白细胞缀合。 EMP-MoC 的特征是识别所涉及的粘附分子及其对单核细胞功能的影响。体内（临床）：与缓解期和对照组相比，恶化期的 EMP-MoC 显着升高，与 GD+ MRI 病变的存在相关。游离 CD54+ EMP 未升高，但游离 CD62E+ EMP 升高。体外：EMP 优先与单核细胞结合，较少与中性粒细胞结合，但与淋巴细胞结合很少。结合 EMP 激活的单核细胞：CD11b 表达增加 50%，穿过脑内皮细胞层的迁移增加 2.6 倍。阻断 CD54 使结合减少 80%。大多数 CD54+ EMP 与单核细胞结合，留下很少的游离 EMP，而 CD62+ EMP 则发现游离和结合。这些结果表明，EMP 的表型亚群与单核细胞的相互作用不同。根据我们的观察，EMP 可能通过 CD54 结合并激活单核细胞，从而增强炎症并增加 MS 中单核细胞的跨内皮迁移。与缓解期相比，MS 恶化期患者的 EMP-MoC 显着升高，可作为 MS 疾病活动的敏感标志物。
Elevated plasma endothelial microparticles (EMP) have been documented in MS during exacerbation. However, the role of EMP in pathogenesis of MS remains unclear. We investigated the formation of EMP-monocyte conjugates (EMP-MoC) and their potential role in transendothelial migration of inflammatory cells in MS. EMP-MoC were assayed in 30 MS patients in exacerbation, 20 in remission and in 35 controls. EMP-leukocyte conjugation was investigated flowcytometrically by employing alpha-CD54 or alpha-CD62E for EMP, and alpha-CD45 for leukocytes. EMP-MoC were characterized by identifying adhesion molecules involved and their effect on monocyte function. In vivo ( clinical): EMP-MoC were markedly elevated in exacerbation vs. remission and controls, correlating with presence of GD+ MRI lesions. Free CD54+ EMP were not elevated but free CD62E+ EMP were. In vitro: EMP bound preferentially to monocytes, less to neutrophils, but little to lymphocytes. Bound EMP activated monocytes: CD11b expression increased 50% and migration through cerebral endothelial cell layer increased 2.6-fold. Blockade of CD54 reduced binding by 80%. Most CD54+ EMP bound to monocytes, leaving little free EMP, while CD62+ EMP were found both free and bound. These results demonstrated that phenotypic subsets of EMP interacted differently with monocytes. Based on our observations, EMP may enhance inflammation and increase transendothelial migration of monocytes in MS by binding to and activating monocytes through CD54. EMP-MoC were markedly increased in MS patients in exacerbation compared to remission and may serve as a sensitive marker of MS disease activity.