Giagulli Cinzia, Scarpini Elio, Ottoboni Linda, Narumiya Shuh, Butcher Eugene C, Constantin Gabriela, Laudanna Carlo
Department of Pathology, Faculty of Medicine, University of Verona, Strada Le Grazie 8, 37134, Verona, Italy.
Immunity. 2004 Jan;20(1):25-35. doi: 10.1016/s1074-7613(03)00350-9.
Chemokines regulate rapid leukocyte adhesion by triggering a complex modality of integrin activation. We show that the small GTPase RhoA and the atypical zeta PKC differently control lymphocyte LFA-1 high-affinity state and rapid lateral mobility induced by chemokines. Activation of LFA-1 high-affinity state and lateral mobility is controlled by RhoA through the activity of distinct effector regions, demonstrating that RhoA is a central point of diversification of signaling pathways leading to both modalities of LFA-1 triggering. In contrast, zeta PKC controls LFA-1 lateral mobility but not affinity triggering. Blockade of the 23-40 RhoA effector region prevents induction of LFA-1 high-affinity state as well as lymphocyte arrest in Peyer's patch high endothelial venules. Thus, RhoA controls the induction of LFA-1 high-affinity state by chemokines independently of zeta PKC, and this is critical to support chemokine-regulated homing of circulating lymphocytes.
趋化因子通过触发整合素激活的复杂模式来调节白细胞的快速黏附。我们发现，小GTP酶RhoA和非典型ζ蛋白激酶C（PKC）对趋化因子诱导的淋巴细胞淋巴细胞功能相关抗原-1（LFA-1）高亲和力状态和快速侧向移动有着不同的调控作用。RhoA通过不同效应区域的活性来控制LFA-1的高亲和力状态和侧向移动，这表明RhoA是导致LFA-1两种激活模式的信号通路多样化的中心点。相比之下，ζ PKC控制LFA-1的侧向移动，但不控制亲和力的触发。阻断23-40 RhoA效应区域可防止LFA-1高亲和力状态的诱导以及淋巴细胞在派尔集合淋巴结高内皮微静脉中的滞留。因此，RhoA独立于ζ PKC控制趋化因子诱导的LFA-1高亲和力状态，这对于支持趋化因子调节的循环淋巴细胞归巢至关重要。
