Chemokines

Dennis D Taub, Clinical Services Program, National Cancer Institute - Frederick Cancer Research and Development Center, Frederick, Maryland, USA

Copyright © 1998 Elsevier Ltd. All Rights Reserved.

The salient feature in a number of inflammatory conditions, such as infection, hypersensitivity reactions or autoimmune diseases, is the presence of infiltrating leukocytes. The extravasating leukocytes are critical for host defense, leading to clearance of the inciting factors such as infectious agents and particulate antigens. However, it should be appreciated that leukocyte recruitment may also contribute to the pathogenesis of an underlying disease. The maintenance of leukocyte recruitment during inflammation requires communication between infiltrating leukocytes and and the endothelium as well as various extravascular cells. These signals are mediated via the generation of early response cytokines, the expression of surface adhesion molecules and the production of chemotactic molecules. While many cytokines modulate cellular adhesion and promote leukocyte recruitment, few have been shown to directly affect integrin avidity. Recent studies have identified a superfamily of small, soluble, structurally-related cytokines called 'chemokines' (chemotactic cytokines) that appear to be excellent, physiologically relevant candidates for the rapid triggering of integrin-mediated adhesion and selectively induce the directional migration of various leukocyte subsets both in vivo and in vitro (Figure 1 and 2). These molecules and their receptors play critical roles in hematopoiesis, angiogenesis, cellular activation, cytotoxicity and wound healing, as well as in a variety of acute and chronic inflammatory disease states.

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