Biology and mechanisms of action of synergistically stimulated myeloid progenitor cell proliferation and suppression by chemokines

Abstract

A number of cytokines can act together to stimulate/enhance the proliferation of hematopoietic stem and progenitor cells in a greater than additive fashion. An example of this is the combination of a colony-stimulating factor with a potent costimulating molecule such as steel factor. Certain members of the chemokine family of cytokines can suppress this synergistically enhanced proliferation. This review focuses on cytokines involved in these stimulating/enhancing/suppressing effects with regard to biological activity and what is beginning to be learned about the intracellular signal transduction events that may he mediating these effects. Examples of intracellular mediators involved include, but are not limited to, the Raf-l/ MAP kinase pathway and cyclin-dependent kinase inhibitors p21ci~-l and for cell proliferation, and eukaryotic initiation factor-4E and 4E hinding protein 1 for protein synthesis. Stem Cells 1997; ~~( S U P P~1): [69][70][71][72][73][74][75][76][77][78]

Simultaneous signalling through c‐mpl, c‐kit and CXCR4 enhances the proliferation and differentiation of human megakaryocyte progenitors: possible roles of the PI3‐K, PKC and MAPK pathways

“…In contrast, other chemokines such as IL‐8 and MIP‐1α have been reported to inhibit megakaryocytopoiesis and myelopoiesis (Gewirtz et al , 1995; Broxmeyer et al , 1997). Taken together, the available data suggest that CXC as well as CC chemokines may positively and/or negatively regulate megakaryocytopoiesis as is the case for myeloid and erythroid progenitor cells (Broxmeyer et al , 1997; Sanchez et al , 1998; Lataillade et al , 2000; Majka et al , 2000). However, the potential biological implications of CXCR4 expression on human megakaryocytic progenitor cells are not yet fully understood.…”

Enhanced Hematopoietic Activity Accompanies Parasite Expansion in the Spleen and Bone Marrow of Mice Infected withLeishmania donovani

“…First, L. donovani infection caused a rapid (5-h), yet transient, increase in progenitor cell frequency in the blood but not the spleen or bone marrow. Rapid mobilization of hematopoietic stem cells and progenitor cells from the bone marrow to the peripheral blood has also been described following the administration of lipopolysaccharide (18), as well as a variety of cytokines, including GM-CSF (42), G-CSF (34,36), SCF (5), , , and MIP-1␣ (6). Although the mechanisms of cytokine-induced cellular mobilization have not been fully elucidated, the modification of adhesive interactions with stromal cells is thought to play a role (40,53).…”

“…Regulation of hematopoietic activity results from many extracellular matrix-cell and cell-cell interactions between a variety of stromal cell populations and hematopoietic stem cells and progenitor cells (7,10,12). This cooperation is mediated through transmembrane adhesion molecules, as well as the production of cytokines and chemokines with hematopoietic activity (2,6,44,47). Alterations in the distribution of hematopoietic activity in the tissues may, however, occur as a result of increased hematopoietic stress.…”

CKβ8-1 alters expression of cyclin E in colony forming units-granulocyte macrophage (CFU-GM) lineage from human cord blood CD34+ cells

“…Although previous studies have reported that several chemokines suppressed the proliferation of progenitor cells, the underlying molecular mechanisms of these chemokines still remain to be established (Broxmeyer et al, 1997;Su et al, 1997;Crow et al, 2001;Han et al, 2003). We also reported that chemokine CKβ8-1 and Lkn-1 suppressed the proliferation of myeloid progenitor cells from human CB (Han et al, 2003; without clarification of functional mechanism of suppression by them.…”