Chemokine receptors and their role in leukocyte activation
Section snippets
Defining the players: new chemokines and their receptors
Chemokines are a large superfamily of small (8–10 kDa) proteins, which are involved in the trafficking and recruitment of leukocytes. The first chemokines to be identified came from cell culture media or leukocyte exudates, and include the two mainstays of chemokine biology, Interleukin-8 (IL-8) [1] and Monocyte Chemoattractant Protein -1 (MCP-1) [2]. Based on the spacings of a pair of amino terminal cysteines, they could be classified into CXC chemokines, and CC chemokines.
By 1995 a second
Modified chemokines as receptor antagonists
Clearly, one of the goals of pharmaceutical research in the chemokine area is to find small molecules which are orally active, as selective anti-inflammatory agents [11]. One set of useful tools that have come out of the work of many groups in the chemokine area, is based on the fact that modifications of the amino terminal region of chemokines has led to receptor antagonists, which often retain partial agonist activity. In our studies, we found that when RANTES is expressed in E. coli, the
Blockade of HIV infection
In late 1995 the chemokine world was shaken up by the discovery that chemokines could modulate infection of host cells by HIV-1 and other primate lentiviruses. Rapidly over the first few months of 1996, the fact that chemokine receptors are required as co-receptors for fusion between the virus and host cells emerged [19], [20]. The fusion of T-tropic HIV-1 viruses with the membrane of the host cell required the presence of CXCR4, whereas the fusion of the M-tropic viruses required CCR5.
Conclusion
Over the last 6 years, our group and many others have worked at trying to define as many as possible of the chemokines and their receptors using a variety of molecular biology techniques. Our hope is that specific inhibition of chemokine receptors using small molecules (which would be orally available therapeutics) will be possible and that will lead to new classes of anti-inflammatory and even anti-retroviral therapy. In the meantime, we have also generated several variants of human chemokines
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2014, Nanomedicine: Nanotechnology, Biology, and MedicineCitation Excerpt :SDF-1α (CXCL12) is a homeostatic chemokine that binds to the chemokine receptor CXCR4 and regulates processes such as hematopoietic cell trafficking and secondary lymphoid organ architecture.44 The CXCR4 receptor in turn plays an important role in homeostasis, cell migration, inflammation, B lymphocyte development and tumor metastasis and is one of the most important co-receptors for HIV.33 To date, only a few works have addressed the effect of metal oxide NPs on chemotactic responses.
Hepatitis B virus X increases immune cell recruitment by induction of chemokine SDF-1
2014, FEBS LettersCitation Excerpt :These results suggest that HBx-induced SDF-1 expression is mediated by XBP1 in the cells. CXCR4 is a GPCR specific to SDF-1 [20,21] and is inhibited by the soluble inhibitor AMD3100. Many recent studies have reported that AMD3100 specifically inhibits SDF-1-mediated responses [22].
Receptor mosaics of neural and immune communication: Possible implications for basal ganglia functions
2008, Brain Research ReviewsCitation Excerpt :Moreover, unlike many cytokine receptors, the repertoire of chemokine receptor expression at the surface of any one cell type is particularly variable, being sensitive to many kinds of cellular activation. Thus, the responsiveness of cells to chemokines is very dependent on the environment to which they have been exposed (Wells et al., 1999). Callewaere et al. (2007) also propose that chemokines can be added to the well-described neuroendocrine regulatory mechanisms, providing an additional fine modulatory tuning system in physiological conditions.
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