Pleiotropic effects of prostaglandin E2 in hematopoiesis; prostaglandin E2 and other eicosanoids regulate hematopoietic stem and progenitor cell function

Abstract

Eicosanoids have been implicated in the physiological regulation of hematopoiesis with pleiotropic effects on hematopoietic stem cells and various classes of lineage restricted progenitor cells. Herein we review the effects of eicosanoids on hematopoiesis, focusing on new findings implicating prostaglandin E2 in enhancing hematopoietic stem cell engraftment by enhancing stem cell homing, survival and self-renewal. We also describe a role for cannabinoids in hematopoiesis. Lastly, we discuss the yin and yang of various eicosanoids in modulating hematopoietic stem and progenitor cell functions and summarize potential strategies to take advantage of these effects for therapeutic benefit for hematopoietic stem cell transplantation.

An emerging link in stem cell mobilization between activation of the complement cascade and the chemotactic gradient of sphingosine-1-phosphate

“…To support this S1P positively regulates activity of cyclooxygenase-2 that is responsible for synthesis of prostaglandin E2 (PGE2) [30, 67]. PGE2 that is also a bioactive lipid has been demonstrated as potent modulator of HSPC trafficking [68–71]. Thus, we have begun to unravel an important regulatory network involving activation of the CC and bioactive lipids that tightly regulate stem cell trafficking, under both steady-state conditions and stress situations.…”

Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation

“…How inflammation-associated PGE 2 alters hematopoietic progenitor cells is a matter of ongoing research although it is clear that hematopoietic stem cells can respond via their EP4 receptor to PGE 2 [11,19,[30][31][32][33]. PGE 2 can stimulate DNA methyltransferases [34] and here we show that the effect of inflammation in the airways on DC progenitors in the BM can be removed by treatment of OVA-sensitized mice with 5-Aza-dC, an inhibitor of DNA methylation.…”

Innate Immunity Derived Factors as External Modulators of the CXCL12 - CXCR4 Axis and Their Role in Stem Cell Homing and Mobilization

“…However, the mechanism of the PGE2 effect on this process is not lipid raft-mediated ( Figure 1 ). Instead, PGE2 plays an important role in homing of HSPCs by upregulating the expression of CXCR4 on the surface of HSPCs, and this seems to be the most likely mechanism responsible for increasing chemotaxis in response to an CXCL12 gradient after pretreatment of HSPCs with PGE2 6, 51, 52.…”