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

Cinzia Giagulli, Elio Scarpini, Linda Ottoboni, Shuh Narumiya, Eugene C. Butcher, Gabriela Constantin, Carlo Laudanna

Research output: Contribution to journalArticle

Abstract

Chemokines regulate rapid leukocyte adhesion by triggering a complex modality of integrin activation. We show that the small GTPase RhoA and the atypical ζ 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, ζ 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 ζ PKC, and this is critical to support chemokine-regulated homing of circulating lymphocytes.

Original languageEnglish
Pages (from-to)25-35
Number of pages11
JournalImmunity
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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