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Immunity. 2004 Jan;20(1):25-35.

RhoA and zeta 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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1
Department of Pathology, Faculty of Medicine, University of Verona, Strada Le Grazie 8, 37134, Verona, Italy.

Abstract

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.

PMID:
14738762
[Indexed for MEDLINE]
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