Chemokines organization

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

The organization of chemokine families based on the cysteine sequence has functional significance. Some human chemokines can compete for binding and activation of receptors with other intrafamily chemokines. This raised the possibility that significant structural differences in chemokine-receptor interactions... 

Forster R, Mattis AE, Kremmer E, Wolf E, Brem G, Lipp M. A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell 1996 87 1037-1047. 

Ansel KM, Ngo VN, Hyman PL, et al. A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 2000 406 309-314. 

Kunkel EJ, Campbell JJ, Haraldsen G, et al. Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. J Exp Med... 

Carramolino L, Zaballos A, Kremer L, et al. Expression of CCR9 beta-chemokine receptor is modulated in thymocyte differentiation and is selectively maintained in CD8(+) T cells from secondary lymphoid organs. Blood 2001 97(4) 850-857. 

Before examining the potential roles of chemokines in the pathophysiology of transplant rejection, it is important to review the biology that underlies the rejection of solid organ allografts. 

Cyster JG. Chemokines and cell migration in secondary lymphoid organs. Science 1999 286(5447) 2098-2102. 

Page G, Lebecque S, Miossec P. Anatomic localization of immature and mature dendritic cells in an ectopic lymphoid organ correlation with selective chemokine expression in rheumatoid synovium. J Immunol 2002 168(10) 5333-5341. 

Chemokines, a superfamily of small (8 to 14 kd) chemoattractant cytokines, were originally identified by their capacity to mediate gradient-dependent cell migration, accompanied by Ca2+ flux, in vitro. Sequence homology of mammal, bird, and fish chemokines indicates that this family of proteins is highly conserved throughout evolution. Chemokines are multifunctional molecules with a vast repertoire of specialized functions in different organs. Broadly, chemokine actions are associated with cell adhesion, cytokine secretion, cellular... 

---