Getting to the site of inflammation: the leukocyte adhesion cascade updated

  title={Getting to the site of inflammation: the leukocyte adhesion cascade updated},
  author={Klaus Ley and Carlo Laudanna and Myron I. Cybulsky and Sussan Nourshargh},
  journal={Nature Reviews Immunology},
Neutrophil recruitment, lymphocyte recirculation and monocyte trafficking all require adhesion and transmigration through blood-vessel walls. The traditional three steps of rolling, activation and firm adhesion have recently been augmented and refined. Slow rolling, adhesion strengthening, intraluminal crawling and paracellular and transcellular migration are now recognized as separate, additional steps. In neutrophils, a second activation pathway has been discovered that does not require… 

Novel aspects in the regulation of the leukocyte adhesion cascade.

The present review will focus on novel aspects with respect to the modulation of the leukocyte adhesion cascade.

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  • D. Vestweber
  • Biology
    Annals of the New York Academy of Sciences
  • 2012
This work has revealed the dominant importance of the junctional pathway between endothelial cells in vivo and improved the understanding of the molecular mechanisms that regulate junctional stability, the opening of endothelial junctions during leukocyte extravasation, and the induction of vascular permeability.

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Signaling through G‐protein‐coupled receptors, selectin ligands, Fc receptors and outside‐in signaling through integrins are all involved in neutrophil activation, but their interplay in the multistep process of recruitment is only beginning to emerge.

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This article revisits some conventional paradigms and selectively highlights new findings, including novel insights into monocyte differentiation and recently identified functional mediators, signalling pathways, and new structural aspects of monocyte extravasation.

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How neutrophil-EC interactions and the subsequent mode of diapedesis, junctional or nonjunctional, can be context dependent and how this plasticity may be exploited clinically is discussed.

Mechanism of Diapedesis: Importance of the Transcellular Route.

  • M. Filippi
  • Biology, Medicine
    Advances in immunology
  • 2016

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The present review will focus on novel aspects with regards to the last step of neutrophil recruitment, namely the transmigration of neutophils through endothelial cells.

Protein tyrosine kinases in neutrophil activation and recruitment.

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The present review aims to provide a brief summary of novel additions to the classical adhesion cascade within the vascular lumen and to discuss the emergence of a secondAdhesion cascade for neutrophils within venular walls, the latter illustrating the intricacies and complexities of neutrophil transmigration.



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Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response.

Mini‐review: Transendothelial migration of leukocytes: through the front door or around the side of the house?

It is proposed that both pathways are equally possible for a leukocyte's journey from the apical surface of the endothelium to its basal side of the vessel wall.

Cell-surface enzymes in control of leukocyte trafficking

New insights are provided into how ectoenzymes — including nucleotidases, cyclases, ADP-ribosyltransferases, peptidase, proteases and oxidases — guide leukocyte traffic.

Rho GTPases and leucocyte-induced endothelial remodelling.

Recent findings on leucocyte-induced alterations to endothelial cells, and the roles of Rho GTPases in these responses are discussed.

The role of JAM‐A and PECAM‐1 in modulating leukocyte infiltration in inflamed and ischemic tissues

Two endothelial junctional proteins [junctional adhesion molecule‐A (JAM‐A) and PECAM], which play an important role in leukocyte diapedesis, are focused on.

Chemokines and the arrest of lymphocytes rolling under flow conditions.

Four chemokines are shown to induce such adhesion to intercellular adhesion molecule-1 and to induce arrest of rolling cells within 1 second under flow conditions similar to those of blood.

Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo.

It is found that CD18 and E-selectin cooperate to control the time a leukocyte needs to roll through an inflamed area and to convert rolling to firm adhesion and leukocytes integrate chemoattractant signals while rolling along the endothelial surface until they reach a critical level of activation and become firmly adherent.

Adhesion mechanisms regulating the migration of monocytes

The signals by which chemokines regulate the leukocyte-adhesion molecules that are essential for transendothelial migration are discussed, and the routes taken by monocytes and myeloid dendritic cells to reach their final destination are described.