Chemokines in hematopoiesis.
OBJECTIVE
Understanding the regulation of hematopoiesis is important for enhanced efficacy of hematopoietic stem and progenitor cell transplantation. Chemokines influence migration, survival, and other actions of hematopoietic stem and progenitor cells. This article summarizes recent progress in understanding the production and actions of chemokines and chemokine receptors, with an emphasis on the SDF-1/CXCL12-CXCR4 axis.


RESULTS
The literature from 2006 to the present is replete with information on SDF-1/CXCL12 activity, including induced intracellular signaling in hematopoietic progenitor cells, lymphocytes, other innate immune cells, breast cancer, and other tumor cells, and on production of SDF-1/CXCL12, and CXCR4, as well as on actions/production of other chemokines. Studies describing these intense research areas are discussed.


CONCLUSIONS
Chemokine-chemokine receptor interactions are important to hematopoiesis and immune cell function, two highly interactive processes. Recent studies have clarified the role of chemokines and their receptors in regulating hematopoiesis, and agents modulating chemokines are being evaluated in preclinical and clinical studies. Examples of such efforts include inhibition of CD26 for enhanced homing and engraftment of hematopoietic stem and progenitor cells, and the use of the SDF-1/CXCL12-CXCR4 antagonist, AMD3100 for mobilization of hematopoietic stem and progenitor cells and their use for stem cell transplantation.
Department of Microbiology and Immunology, and Walther Oncology Center, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202, USA. hbroxmey@iupui.edu
Hal E
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Broxmeyer
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12 / Q000502:physiology; D018925:Chemokines / Q000502:physiology*; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D016131:Lymphocyte Subsets / Q000166:cytology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000166:cytology; D019718:Receptors, CXCR4 / Q000502:physiology; D019707:Receptors, Chemokine / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
C515255:CXCL12 protein, human; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D018925:Chemokines; C515256:Cxcl12 protein, mouse; D054873:Dipeptidyl-Peptidase IV Inhibitors; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4