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Journal of Molecular Medicine

, Volume 90, Issue 4, pp 353–359 | Cite as

Leukocyte integrin activation and deactivation: novel mechanisms of balancing inflammation

  • Alexander Zarbock
  • Tibor Kempf
  • Kai C. Wollert
  • Dietmar Vestweber
Review

Abstract

Leukocyte recruitment into tissue forms the basis of immune surveillance and direct immune defense. It proceeds in a cascade-like fashion. The first contact of leukocytes with the endothelium is mediated by selectins and their counter receptors, followed by rolling and integrin-mediated arrest. While rolling, neutrophils collect different inflammatory signals which can activate several signaling pathways leading to leukocyte adhesion to the endothelium and transmigration through the blood vessel wall into the inflamed tissue. Whereas inflammatory reactions are beneficial and necessary for host defense, they need to be balanced and controlled to prevent harmful consequences and tissue destruction. In this article, we discuss the different signaling pathways that ensure rapid and efficient integrin activation on leukocytes. In addition, we report on a recently identified novel endogenous mechanism that counteracts and balances integrin activation, thereby limiting leukocyte recruitment and the extent of inflammation. Further investigation of this new mechanism may allow providing new approaches for the development of the next generation of anti-inflammatory drugs.

Keywords

Selectin Chemokin Integrin regulation Signaling GDF-15 

Notes

Acknowledgment

This study is supported by grants from the German Research Foundation (AZ 428/3-1 and AZ 428/6-1 to A.Z.) and the Interdisciplinary Clinical Research Center (IZKF Muenster, Germany, Za2/001/10 to A.Z.).

Disclosure statement

The authors declare no conflict of interest related to this study.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Alexander Zarbock
    • 1
    • 2
  • Tibor Kempf
    • 3
  • Kai C. Wollert
    • 3
  • Dietmar Vestweber
    • 2
  1. 1.Department of Anesthesiology and Intensive Care MedicineUniversity of MünsterMünsterGermany
  2. 2.Max-Planck Institute for Molecular BiomedicineMünsterGermany
  3. 3.Molecular and Translational Cardiology, Department of Cardiology and AngiologyHannover Medical SchoolHannoverGermany

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