Integrin activation by chemokines: relevance to inflammatory adhesion cascade during T cell migration.
The adhesive function of integrins is regulated through cytoplasmic signaling induced by several stimuli, whose process is designated "inside-out signaling". A large number of leukocytes are rapidly recruited to the sites of inflammation where they form an essential component of the response to infection, injury, autoimmune disorders, allergy, tumor invasion, atherosclerosis and so on. The recruitment of leukocytes into tissue is regulated by a sequence of interactions between the circulating leukocytes and the endothelial cells. Leukocyte integrins play a pivotal role in leukocyte adhesion to endothelial cells. During the process, the activation of integrins by various chemoattractants, especially chemokines, is essential for integrin-mediated adhesion in which a signal transduced to the leukocyte converts the functionally inactive integrin to an active adhesive configuration. We have proposed that H-Ras-sensitive activation of phosphoinositide 3 (PI 3)-kinase and subsequent profilin-mediated actin polymerization, can be involved in chemokine-induced integrin-dependent adhesion of T cells. The present review documents the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemoattractants including chemokines during inflammatory processes. In contrast, various adhesion molecules are known to transduce extracellular information into cytoplasm, which leads to T cell activation and cytokine production from the cells, designated "outside-in signaling". Such a bi-directional "cross-talking" among adhesion molecules and cytokines is most relevant to inflammatory processes by augmenting immune cell migration from circulation into inflamed tissue such as rheumatoid arthritis, tumor invasion, Behçet's disease and atherosclerosis.
Tanaka
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The First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan. tanaka@med.uoech-u.ac.jp
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D018925:Chemokines / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D016023:Integrins / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology*
D018925:Chemokines; D016023:Integrins