RhoA and ζ PKC control distinct modalities of LFA-1 activation by chemokines:: Critical role of LFA-1 affinity triggering in lymphocyte in vivo homing
RhoA and ζ PKC control distinct modalities of LFA-1 activation by chemokines:: Critical role of LFA-1 affinity triggering in lymphocyte in vivo homing
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DOI：
10.1016/s1074-7613(03)00350-9
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发表时间：
2004-01-01
期刊：
影响因子：
32.4
通讯作者：
Laudanna, C
中科院分区：
文献类型：
--
作者：
Giagulli, C;Scarpini, E;Laudanna, C
趋化因子通过触发整合素激活的复杂方式来调节白细胞的快速粘附。我们发现小 GTP 酶 RhoA 和非典型 zeta PKC 不同地控制趋化因子诱导的淋巴细胞 LFA-1 高亲和力状态和快速横向移动。 LFA-1 高亲和力状态和横向移动性的激活由 RhoA 通过不同效应器区域的活动控制，表明 RhoA 是导致 LFA-1 两种触发方式的信号通路多样化的中心点。相反，PKC 控制 LFA-1 横向移动性，但不控制亲和力触发。封锁 23-40 RhoA 效应区可防止诱导 LFA-1 高亲和力状态以及派尔氏集结高内皮场所中的淋巴细胞停滞。因此，RhoA 独立于 PKC 控制趋化因子对 LFA-1 高亲和力状态的诱导，这对于支持趋化因子调节的循环淋巴细胞归巢至关重要。
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, 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 venues. Thus, RhoA controls the induction of LFA-1 high-affinity state by chemokines independently of PKC, and this is critical to support chemokine-regulated homing of circulating lymphocytes.