Rapid leukocyte integrin activation by chemokines.

Abstract:

:Chemokines control selective targeting of circulating leukocytes to the microvasculature by triggering inside-out signal transduction pathways leading to integrin-dependent adhesion. Integrin activation by chemokines is very rapid, is downmodulated within minutes and appears to involve both enhanced heterodimer lateral mobility on the plasma membrane, facilitating encounters with dispersed ligand, as well as induction of a high-affinity state. These two modalities of integrin activation by chemokines involve distinct signaling pathways in the cell, yet complement each other functionally, allowing binding of rolling cells under conditions of low as well as high ligand density. Recent data show that chemokines generate both pro- and anti-adhesive intracellular signaling events, whose equilibrium is likely to be relevant to the kinetics of adhesion and de-adhesion, and to cell movement during diapedesis and chemotaxis. Importantly, chemokines utilize different signaling mechanisms to modulate the activity of distinct integrin subtypes. These recent advances suggest that chemokines may regulate adhesive responses of immune cells based not only on patterns of chemokine receptor expression, but also on variable signaling pathways that can modulate the pro-adhesive responses of leukocytes as a function of their differentiated state, and of the local microenvironment.

journal_name

Immunol Rev

journal_title

Immunological reviews

authors

Laudanna C,Kim JY,Constantin G,Butcher E

doi

10.1034/j.1600-065x.2002.18604.x

keywords:

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

37-46

eissn

0105-2896

issn

1600-065X

pii

imr18604

journal_volume

186

pub_type

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