Signaling Pathways Involved in Leukocyte Adhesiveness and Migration during Inflammation: Potential Targets for Therapeutic Interventions?

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)


Volume 15, 3 Issues, 2016


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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Editor-in-Chief:
Claudiu T. Supuran
Neurofarba Department
University of Florence
Florence
Italy


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Signaling Pathways Involved in Leukocyte Adhesiveness and Migration during Inflammation: Potential Targets for Therapeutic Interventions?



Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 5(1): 59-69.

Author(s): Christina Barja-Fidalgo, Maria A. C. Arruda, Roberta Saldanha-Gama and Marta S de Freitas.

Affiliation: Departamento de Farmacologia,IBRAG, UERJ. Av 28 de setembro 87 fds, Vila Izabel, Rio de Janeiro,RJ 20551-030, Brazil.

Abstract

In response to a chemotactic gradient of inflammatory mediators and chemokines, neutrophils adhere to vascular endothelium and directly migrate, leaving blood vessels, toward inflamed tissue areas, to exert their primary defense function. These events are mediated by distinct classes of cell surface receptors in human neutrophils, that not only drive cell adhesion and motility, but also interfere with the cells activation status, modulating different functions and survival. In this review we summarize the current understanding of the series of events that begins at the level of G-protein coupled receptor activation by chemoattractants, and the signaling pathways triggered by cell adhesion molecule interactions that lead to neutrophil adhesion, migration and activation during inflammation. Integrins, as adhesion receptors able to act as anchoring molecules (allowing firm cellular attachment to the ECM) and signaling receptors (transducing signals in both directions, outside-in and inside-out) are targets that potentially provide both therapeutic and diagnostic opportunities. We also present data obtained with integrin-selective ligands, the disintegrins, which could be useful tools to understand cellular processes as adhesion, migration, proliferation, activation and cell survival and may be also suggested as prototypes for designing therapeutic agents for the prevention or activation of integrin-mediated effects.

Keywords:

Adhesion molecules, neutrophils, migration, adhesion, activation, chemotaxis, intracellular signaling pathways, integrin, disintegrin.



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Article Details

Volume: 5
Issue Number: 1
First Page: 59
Last Page: 69
Page Count: 11
DOI: 10.2174/187152306775537283
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