Hematopoiesis, chemokines

Beyond roles of chemokine receptors in hematopoiesis and innate immunity, roles for chemokines in adaptive immunity emerged. Moreover, other nonleukocyte migration properties of chemokine receptors have been identified. These include roles in the biology of endothelial cells (Chapter 15), cancer (Chapter 16), smooth muscle (Chapter 11), fibroblasts (Chapter 14), stem cells (Chapter 8), and all cell types associated with nervous system tissues (Chapter 17). In many instances, broad functional overlap is evident as chemokines can direct the migration of these cells just as they do with leukocytes. In certain instances, the ability of chemokines to retain cell populations within a specific microenvironment is as important as their migration-promoting properties. However, it is also clear that migration and retention are not the sole end points. 

Gao J-L, Wynn TA, Chang Y, et al. Imparted host defense, hematopoiesis, granulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1. J Exp Med 1997 185 1959-1968. 

Chemokines in Trafficking of Hematopoietic Stem and Progenitor Cells and Hematopoiesis... 

Key Words Stem cells chemokines hematopoiesis chemotaxis T cells B cells. 

Broxmeyer HE, Kim CH. Regulation of hematopoiesis in a sea of chemokine family members with a plethora of redundant activities. Exp Hematol 1999 27(7) 1113—1123. 

Production of blood cells in bone marrow of the central axial skeleton is referred to as medullary hematopoiesis. Hematopoietic tissue in adult bone marrow is well perfused and contains fat cells (adipocytes), and various types of blood and blood precursor cells encased within a protein matrix. Fibroblast, stromal and endothelial cells within bone marrow, serve as sources of matrix proteins as well as a factory for growth factors and chemokines that regulate blood cell production and release matured cells into the circulation [2,3]. Chemokines act as signal lamps for trafficking of lymphocytes in and out of lymphoid tissues. Erythroblasts, neutrophils, lymphoblasts, macrophages, megakaryocytes, and pluripotent stem cells are also found within the calcihed lattice crisscrossing the marrow space. 

Chemokines have been implicated in diverse pathophysiological functions in allergic inflammation including chemoattraction, cellular activation, hematopoiesis, homeostatic role, and modulation of T cell immune response (R6). 

Numerous and diverse biological functions are regulated by chemokines. In addition to the well characterized proinflammatory activities such as integrin activation, chemotaxis, lipid mediator biosynthesis, superoxide radical production, and granule enzyme release (reviewed in refs. 1-4), chemokines have been shown to suppress and stimulate angiogenesis (5-7), suppress hematopoiesis (8-10), suppress apoptosis (11), control viral infection (12,13), and effect leukocyte differentiation (14). Among the proinflammatory activities, chemotaxis in particular has received considerable attention as a target for novel antiinflammatory therapeutics (reviewed in ref. 15). 

As the number of chemokines and receptors continue to expand so too does the list of ascribed biological functions. Beyond their characterized roles in leukocyte trafficking and inflammation, chemokines have been shown to effect angiogenesis (24-26), hematopoiesis (27-29), T-cell differentiation (30), apoptosis (31), and viral infection (32,33), although the biological significance of these effects as well as the mechanism of action remain to be determined in many cases. Furthermore, chemokine receptor expression has been reported on nonlymphoid cell types in brain and vasculature (34,35). Antibodies will no doubt prove to be useful in determining the function of these receptors in other systems. 

In animal models, the lack of either SDF-1 or CXCR4 exhibits an almost identical phenotype of late gestational lethality and defects in B cell lymphopoiesis, bone marrow colonization, and cardiac septum formation [13, 14]. These studies indicated that CXCR4 is essential for development, hematopoiesis, organogenesis, and vascularization [13-19], in addition to functioning as a classical chemokine receptor in adults [5, 19]. 

Nagasawa T., Tachibana K., and Kishimoto T. (1998) A novel CXC chemokine PBSF/ SDF-1 and its receptor CXCR4 their functions in development, hematopoiesis and HIV infection. Semin Immunol., 10, 179-85. 

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