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Rapid leukocyte integrin activation by chemokines
Carlo Laudanna1, Ji Yun Kim, Gabriela Constantin
1Section of General Pathology, Department of Pathology, Faculty of Medicine, University of Verona, 37138, Verona, Italy. carlo.laudanna@univr.it
Immunological Reviews
|September 18, 2002
Summary
Chemokines rapidly activate leukocyte integrins through distinct signaling pathways, influencing cell adhesion and movement. This process involves both enhanced mobility and high-affinity states, crucial for immune cell targeting.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Chemokines orchestrate leukocyte trafficking by initiating inside-out signaling cascades that activate integrins.
- Integrin activation by chemokines is a rapid, transient process involving enhanced lateral mobility and induction of high-affinity states.
Purpose of the Study:
- To elucidate the distinct signaling pathways and functional roles of chemokine-mediated integrin activation.
- To understand how chemokines modulate leukocyte adhesion under varying ligand densities and cellular conditions.
Main Methods:
- The study integrates findings from signaling pathway analysis and cell adhesion assays.
- Investigated the interplay between intracellular signaling events and integrin function.
Main Results:
- Chemokine-induced integrin activation involves both enhanced heterodimer mobility and a high-affinity state, mediated by distinct signaling pathways.
- Chemokines generate opposing intracellular signals (pro- and anti-adhesive) that regulate adhesion kinetics, de-adhesion, and cell migration during diapedesis and chemotaxis.
- Different chemokines employ unique signaling mechanisms to modulate specific integrin subtypes.
Conclusions:
- Chemokines finely tune leukocyte adhesion through complex signaling networks, impacting immune cell responses.
- Leukocyte adhesion regulation is influenced by chemokine receptor expression, signaling pathway variability, and the microenvironment.