Protein tyrosine kinases in neutrophil activation and recruitment

doi:10.1016/j.abb.2011.02.009

Archives of Biochemistry and Biophysics

Volume 510, Issue 2, 15 June 2011, Pages 112-119

https://doi.org/10.1016/j.abb.2011.02.009 Get rights and content

Abstract

Migration of leukocytes into tissue is a key element of innate and adaptive immunity. The first contact of leukocytes with endothelial cells is mediated by engagement of selectins with their counter-receptors which results in leukocyte rolling. During rolling, leukocytes collect different inflammatory signals that activate intracellular signaling pathways. Integration of these signals induces leukocyte activation, firm arrest, post-adhesion strengthening, intravascular crawling, and transmigration. In neutrophils, like in T-cells and platelets, both G-protein-coupled receptor-dependent and -independent activation pathways exist that lead to integrin activation. Accumulating evidence suggests that different protein tyrosine kinases play key roles in signal transduction pathways regulating neutrophil activation and recruitment to inflammatory sites. This review focuses on the role of protein tyrosine kinases of the Src, Syk, and Tec families for neutrophil activation and recruitment.

Research highlights

► Protein tyrosine kinases (PTK) are involved in neutrophil activation and recruitment. ► PTKs participate in signaling downstream of PSGL-1 and β₂-integrins in neutrophils. ► Some PTKs have redundant functions, whereas other PTKs have unique functions.

Introduction

The immune system consists of a complex network of cells and molecules that work together in order to shelter the body from viral, bacterial, fungal and parasitic infections. A fundamental feature of any immune response is the movement of immune cells from the blood to tissues in order to provide effector function. Leukocyte recruitment from the blood into peripheral tissue or lymph nodes is tightly regulated. Neutrophils are often the first responders to be recruited to sites of inflammation. A disruption of this process leads to an altered immune response [1], [2]. New evidence suggests that at least three families of protein tyrosine kinases are implicated in signal transduction pathways regulating neutrophil function and recruitment into inflamed tissue.

Section snippets

Leukocyte recruitment

Leukocyte recruitment into inflamed tissue proceeds in a cascade-like fashion including capturing, rolling, slow rolling, arrest, post-adhesion strengthening, intravascular crawling, and paracellular or transcellular transmigration [3]. Interaction of selectins with their counter-receptors mediates capturing and rolling of leukocytes on inflamed endothelium and, together with chemokines, regulate integrin adhesiveness. Binding of activated integrins to their counter-receptors mediates,

Immunoreceptor signaling

The T-cell receptor, B-cell receptor, Fc receptors, and activating receptors of natural killer (NK) cells belong to the classical immunoreceptors. Although these receptors have different ligands, their intracellular signaling pathways are highly conserved [55], [56], [57], [58]. Depending on the cell type, activation of immunoreceptors by ligand binding induces the activation of different Src-family kinases including c-Src, c-Yes, Lck, Fyn, Lyn, c-Fgr, Blk, and Hck. Activated Src kinases

Protein tyrosine kinases in neutrophil recruitment

The importance of the tyrosine phosphorylation cascade in the initiation and regulation of neutrophil recruitment and functional responsiveness is well established. In addition to the immunoreceptor signaling, the different protein tyrosine kinases expressed in neutrophils also participate in a variety of cell functions. Here, we focus on the role of the protein tyrosine kinases Src-family kinases, Syk, and Tec kinases for leukocyte recruitment and function.

Conclusion

The Src, Syk, and Tec family of kinases are essential for signaling immediately downstream of PSGL-1 and β₂-integrins in neutrophils. New in vitro and in vivo studies provide a better understanding of how these kinases are activated and involved in regulating neutrophil activation and recruitment in response to different stimuli. The current data are consistent with a model in which some protein tyrosine kinases have a unique function in neutrophil activation, whereas other protein tyrosine

Acknowledgments

A.Z. is supported by grants from the German Research Foundation (DFG AZ 428/3-1, AZ 428/5-1) and the Interdisciplinary Clinical Research Center (IZKF, ZA2/001/10) (Muenster, Germany).

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Protein tyrosine kinases in neutrophil activation and recruitment

Abstract

Research highlights

Introduction

Section snippets

Leukocyte recruitment

Immunoreceptor signaling

Protein tyrosine kinases in neutrophil recruitment

Conclusion

Acknowledgments

Curr. Opin. Cell Biol.

Cell

J. Vasc. Surg.

Immunity

Blood

Cell

Blood

Cell

Blood

Immunity

Am. J. Pathol.

J. Mol. Biol.

Immunity

Blood

Cell

Immunity

Semin. Immunol.

Trends Immunol.

Cell. Signal.

Blood

Immunity

Blood

Blood

Immunol. Today

Cell

Curr. Opin. Chem. Biol.

Biochem. Biophys. Res. Commun.

Mol. Immunol.

Trends Biochem. Sci.

Biochim. Biophys. Acta

Blood

Blood

Blood

Immunity

Immunol. Today

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Immunity

Immunol. Lett.

Trends Immunol.

Annu. Rev. Med.

Nat. Rev. Immunol.

Nat. Rev. Immunol.

J. Exp. Med.

Annu. Rev. Immunol.

Cell Adhes. Commun.

J. Clin. Invest.

J. Clin. Invest.

J. Exp. Med.