Institute for Experimental Physics, Ulm University, Ulm, Germany.
Department of Neurology, Ulm University, Ulm, Germany.
Sci Rep. 2017 May 17;7:46532. doi: 10.1038/srep46532.
Adhesion of monocytes to micro-injuries on arterial walls is an important early step in the occurrence and development of degenerative atherosclerotic lesions. At these injuries, collagen is exposed to the blood stream. We are interested whether age influences monocyte adhesion to collagen under flow, and hence influences the susceptibility to arteriosclerotic lesions. Therefore, we studied adhesion and rolling of human peripheral blood monocytes from old and young individuals on collagen type I coated surface under shear flow. We find that firm adhesion of monocytes to collagen type I is elevated in old individuals. Pre-stimulation by lipopolysaccharide increases the firm adhesion of monocytes homogeneously in older individuals, but heterogeneously in young individuals. Blocking integrin α showed that adhesion of monocytes to collagen type I is specific to the main collagen binding integrin αβ. Surprisingly, we find no significant age-dependent difference in gene expression of integrin α or integrin β. However, if all integrins are activated from the outside, no differences exist between the age groups. Altered integrin activation therefore causes the increased adhesion. Our results show that the basal increase in integrin activation in monocytes from old individuals increases monocyte adhesion to collagen and therefore the risk for arteriosclerotic plaques.
单核细胞黏附在动脉壁上的微损伤是退行性动脉粥样硬化病变发生和发展的重要早期步骤。在这些损伤中，胶原暴露于血流中。我们感兴趣的是年龄是否会影响单核细胞在流动状态下黏附于胶原，从而影响动脉粥样硬化病变的易感性。因此，我们研究了在剪切流条件下，来自老年人和年轻人外周血单核细胞在胶原 I 涂层表面上的黏附和滚动。我们发现老年人单核细胞与胶原 I 的牢固黏附增加。脂多糖预处理均匀增加老年人单核细胞的牢固黏附，但在年轻人中则不均匀。阻断整合素 α 表明单核细胞与胶原 I 的黏附特异性地与主要的胶原结合整合素 αβ 有关。令人惊讶的是，我们没有发现整合素 α 或整合素 β 的基因表达与年龄相关的显著差异。然而，如果所有整合素都从外部激活，则年龄组之间没有差异。因此，整合素激活的改变导致黏附增加。我们的结果表明，老年人单核细胞中基础整合素激活的增加增加了单核细胞对胶原的黏附，从而增加了动脉粥样硬化斑块的风险。
