Department of Anesthesiology and Intensive Care Medicine, University of Münster, Münster, Germany.
Kidney Int. 2011 Sep;80(5):493-503. doi: 10.1038/ki.2011.125. Epub 2011 May 11.
Acute loss of renal function reduces leukocyte recruitment into inflamed tissues, and we studied the molecular basis of this using intravital microscopy of cremaster muscle and an autoperfused flow chamber system after bilateral nephrectomy or sham operation in mice. Acute loss of renal function resulted in cessation of selectin-induced slow leukocyte rolling on E-selectin/intercellular adhesion molecule 1 (ICAM-1) and P-selectin/ICAM-1. It also reduced in vivo neutrophil extravasation (assessed by reflected light oblique transillumination) without affecting chemokine-induced arrest. This elimination of selectin-mediated slow leukocyte rolling was associated with a reduced phosphorylation of spleen tyrosine kinase, Akt, phospholipase C-γ2, and p38 MAPK. However, the levels of adhesion molecules located on the neutrophil surface were not altered. Leukocytes from critically ill patients with sepsis-induced acute kidney injury showed a significantly higher rolling velocity on E-selectin/ICAM-1- and P-selectin/ICAM-1-coated surfaces compared with patients with sepsis alone or healthy volunteers. Thus, an acute loss of renal function significantly impairs neutrophil rolling and transmigration, both in vivo and in vitro. These effects are due, in part, to decreased phosphorylation of selectin-dependent intracellular signaling pathways.
急性肾功能丧失会减少白细胞向炎症组织的募集，我们使用盲肠肌肉的活体显微镜检查和双侧肾切除或假手术小鼠的自体灌注流动室系统研究了这种现象的分子基础。急性肾功能丧失导致选择素诱导的白细胞在 E-选择素/细胞间黏附分子 1 (ICAM-1) 和 P-选择素/ICAM-1 上的缓慢滚动停止。它还减少了体内中性粒细胞渗出（通过反射光斜透射光评估），而不影响趋化因子诱导的阻滞。这种选择素介导的缓慢白细胞滚动的消除与脾酪氨酸激酶、Akt、磷脂酶 C-γ2 和 p38 MAPK 的磷酸化减少有关。然而，位于中性粒细胞表面的粘附分子的水平没有改变。与单独患有败血症或健康志愿者相比，患有败血症诱导的急性肾损伤的危重病患者的白细胞在 E-选择素/ICAM-1 和 P-选择素/ICAM-1 涂层表面上的滚动速度明显更高。因此，急性肾功能丧失会显著损害中性粒细胞的滚动和迁移，无论是在体内还是在体外。这些影响部分归因于选择素依赖性细胞内信号通路的磷酸化减少。
