Kuijper P H, Gallardo Torres H I, Houben L A, Lammers J W, Zwaginga J J, Koenderman L
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
J Leukoc Biol. 1998 Oct;64(4):467-73. doi: 10.1002/jlb.64.4.467.
Accumulation of monocyte-derived foam cells in focal areas of the atherosclerotic (A.S.-) lesion is one of the key events in early atherogenesis. Using a flow model for the damaged vessel wall, we examined the ability of ECM-bound platelets to induce monocyte tethering and adhesion. Whereas ECM-proteins alone induced monocyte adhesion only at low shear stresses (< 100 mPa), ECM-bound platelets induced monocyte rolling and adhesion at shear stresses up to 240 mPa. Studies with specific antibodies showed that monocyte adhesion to platelets was mainly mediated by P-selectin and monocyte PSGL-1 (maximum inhibition 90%). beta2-Integrin blocking CD18 and CD11b antibodies partly inhibited the arrest of rolling cells. Antibodies against other adhesion molecules such as LFA-1, PECAM-1, and beta1-integrins had no effect. Even sparsely adhered platelets (approximately 10% coverage of the surface) already strongly supported monocyte tethering. In conclusion, activated platelets present on ECM are a powerful adhesive substrate for monocyte recruitment under flow conditions.
单核细胞源性泡沫细胞在动脉粥样硬化（A.S.）病变的局部区域积聚是早期动脉粥样硬化形成的关键事件之一。我们使用受损血管壁的流动模型，研究了细胞外基质（ECM）结合的血小板诱导单核细胞系留和黏附的能力。单独的ECM蛋白仅在低剪切应力（<100 mPa）下诱导单核细胞黏附，而ECM结合的血小板在高达240 mPa的剪切应力下诱导单核细胞滚动和黏附。使用特异性抗体的研究表明，单核细胞与血小板的黏附主要由P-选择素和单核细胞PSGL-1介导（最大抑制率90%）。阻断CD18和CD11b的β2整合素抗体部分抑制滚动细胞的停滞。针对其他黏附分子如LFA-1、PECAM-1和β1整合素的抗体没有作用。即使是稀疏黏附的血小板（表面覆盖率约10%）也已经强烈支持单核细胞系留。总之，存在于ECM上的活化血小板是流动条件下单核细胞募集的强大黏附底物。
