Chemokine-mediated migration leukocytes

The chemotaxis of mononuclear leukocytes and the migration, growth, and activation of the multiple cell types within atherosclerotic lesions are critical for the chronic inflammatory and fibroproliferative response in atherosclerosis (Ml). Chemokine-mediated attraction of leukocytes to tissues has been shown in atherosclerotic lesions (G8). Studies using knockout and transgenic murine models indicated that chemokine receptor/ligand interactions are crucial in the development of atherosclerosis (P6). Moreover, chemokines may also interfere with smooth muscle cell migration and growth, and platelet activation and other well-defined features of the atherosclerotic process (A2). 

Figure 31.5. Leukocyte migration into focally ischemic brain. Histologic and schematic representations of changes in leukocyte behavior in die brain microvessels after focal ischemia. Shortly (widhn l-6h) after experimental stroke, many of die leukocytes, primaiily neuti ophils, in die ischemic dssue vessels are adherent to die post-capillai y venuole and capillai y walls. Tliis can modify and exacerbate die decreased blood flow occuriing in die already ischemic brain. Tlien, diese neuti ophils can find dieir way outside die vascular walls into die focal ischemic cortex over die next 6-24h. Macrophages move into die brain later (i.e., over 1—5 days) and significantly accumulate in die infai cted brain. These changes in leukocyte behavior ai e mediated by increased brain inflammatory cytokine, adliesion molecule(s), and chemokine expression in die ischemic/injured brain. Reproduced from ref Barone FC, Feuerstein GZ. Inflammatory mediators and stroke new opportunities for novel therapeutics. J Cereb Blood Flow Me tab 1999 19 819-834. With permission from Nature.

The chemokine receptors are a diverse family of seven-transmembrane G-protein-coupled receptors binding a large family of ligands. Chemokine receptors were first identified on leukocytes and mediate directed migration of many host cells to sites of ligand expression. It is now well established that most malignant cells also express one or more chemokine receptor. This volume will summarize the growing body of evidence that several chemokine receptors contribute to tumor behavior. 

Chemokines are a large family of proteins that mediate the directed migration of leukocytes in the body. The moderate size ( 70 amino acids) and medical importance of these proteins have made them an attractive target for chemical... 

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