Chemokines, chemokine receptors and hematopoiesis

Abstract

Hematopoiesis during steady state conditions is regulated and finely tuned by a network of cytokines and their effects on hematopoietic stem and progenitor cells and on accessory cells that influence the stem and progenitor cells. Amongst the numerous cytokines implicated in this regulation are members of the CC, CXC and C family of chemokines. Twenty-five chemokine members have been demonstrated to have the capacity to suppress the proliferation of myeloid progenitor cells. Three chemokines have been implicated in the chemotaxis of these stem and progenitor cells, and one has been linked to their survival after growth factor withdrawal. This review focuses on the proliferation-suppressing, chemotaxis-induced, and cell survival effects of different chemokine family members on myeloid progenitor cells. This is placed in the context of what we know and don't know about the intracellular signaling events mediating these effects. This information and what is yet to be learned in this area could have important clinical implications for treatment of disease.

Transgenic Expression of Stromal Cell-Derived Factor-1/CXC Chemokine Ligand 12 Enhances Myeloid Progenitor Cell Survival/Antiapoptosis In Vitro in Response to Growth Factor Withdrawal and Enhances Myelopoiesis In Vivo

“…Moreover, the use of PTX clearly demonstrated that the survivalenhancing effect was mediated through G␣i proteins. SDF-1/ CXCL12 as well as other chemokines are known to mediate their chemotactic effects for myeloid progenitors and other more mature cells through G ␣i proteins (5)(6)(7)(8)21). To establish additional controls for the enhanced survival of RSV-SDF-1/CXCL12 transgenic myeloid progenitors, we tested the survival of bone marrow and spleen cells from other transgenic mice we produced in which SDF-1/CXCL12 transgene expression was under the control of an LCK promoter (30), which limited expression of the SDF-1/ CXCL12 transgene to lymphoid cells (data not shown).…”

CXCR4-mediated Suppressor of Cytokine Signaling Up-regulation Inactivates Growth Hormone Function

“…It has been established that hematopoietic cell growth, differentiation, and function are controlled by the coordinated action of the cytokine-chemokine network (47). All leukocyte lineages are derived from pluripotent hematopoietic stem cells (HSC) that localize predominantly in the fetal liver and adult bone marrow.…”

Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse

“…The elaboration of chemokines and expression patterns of their receptors is known to be critical for cellular homing into and out of sites of inflammation (18). Notably, CCR4 expression identified a markedly diabetogenic T cell population, and the transfer of these cells precipitated severe diabetes in naïve NOD recipients (S.-H.K.…”

“…To investigate potential lymphocyte recruitment signals differentiating CD1 Ϫ/Ϫ NOD and CD1 ϩ/ϩ NOD mice, an analysis of T cell CCR and endothelial adhesion molecule expression was undertaken (18). A fluorescence-activated cell sorter analysis of lymphocytes purified from the peripheral lymphoid organs and pancreata was done to determine CCR status for chemokine receptors CCR3, CCR4, and CCR5, whose increased cell-surface expression or intraislet concentration of ligand were associated with increased diabetogenicity (ref.…”