Eicosanoid regulation of hematopoiesis and hematopoietic stem and progenitor trafficking

Hoggatt, Jonathan; Pelus, Louis M.

doi:10.1038/leu.2010.216

Cited by 97 publications

(95 citation statements)

References 141 publications

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“…33 An inhibitory effect of PGE 2 on proliferation of myeloid progenitor cells in agar cultures was described in 1979. 34,35 A concentration of PGE 2 as low as 10 Ϫ10 M was reported to inhibit macrophage-colony proliferation on agar cultures. 34 Subsequently, PGE 2 has been shown to suppress differentiation of dendritic cells via EP2 36 or EP4 37 receptors.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 restrains macrophage maturation via E prostanoid receptor 2/protein kinase A signaling

Zasłona

Serezani

Okunishi

et al. 2012

Blood

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IntroductionMononuclear phagocytes play a vital role in innate immune defense 1 and in disease states such as diabetes, 2 atherosclerosis, 3 and emphysema. 4 The mononuclear phagocyte system encompasses both circulating peripheral blood monocytes and tissue macrophages. 5 It is generally believed that monocytes and macrophages originate from a common myeloid precursor in the bone marrow. 6 Tissue macrophages may derive from either local proliferation or from recruitment of peripheral monocytes. Although local proliferation may play a role under steady-state conditions, repopulation of resident tissue macrophages in the setting of inflammation is more dependent on the recruitment of precursor cells from the blood. 7 After emigrating from the blood to the tissues, monocytes continue the process of maturation and undergo the final differentiation steps necessary to become a macrophage. 8 Macrophage maturation also has been studied in vitro, with a commonly used protocol consisting of bone marrow cells cultured in the presence of macrophage colony-stimulating factor (M-CSF). This in vitro approach results in a high yield of relatively homogenous primary macrophages that are not conditioned by the tissue microenvironment.Prostaglandin E 2 (PGE 2 ) is a lipid mediator derived from the metabolism of arachidonic acid by cyclooxygenase (COX). It is the most abundant prostanoid in most tissues, and it is a well-known regulator of numerous physiologic and pathophysiologic processes, including blood flow, 9 parturition, 10 fever, and cancer and inflammation. 11 PGE 2 exerts its actions through 4 different types of G protein-coupled receptors called E prostanoid (EP) receptors 1 to 4. PGE 2 has diverse effects on differentiation, migration, and activation of immune cells, including lymphocytes, dendritic cells, and macrophages. Its effects on macrophage functions have been amply documented to be mainly suppressive, 12,13 reflecting an increase in the levels of the intracellular second messenger cAMP generated on ligation of EP2 and EP4 receptors. 14 By contrast, there is little known about the role of PGE 2 /cAMP in macrophage maturation. Questions of how PGE 2 affects macrophage maturation, whether endogenously generated PGE 2 modulates this process, the role of specific EP receptors in such effects, and whether PGE 2 influences macrophage maturation in vivo remain unanswered.Here, we have used pharmacologic and genetic approaches to determine the role of PGE 2 /EP2 signaling in the regulation of macrophage maturation in vitro and in vivo. We report that PGE 2 /EP2 signaling suppresses macrophage maturation, and we have characterized key afferent and efferent mechanisms for this effect. Because PGE 2 production is altered by both disease states and medications, and because maturation status influences macrophage functions, these findings have broad implications. Methods AnimalsMice harboring a targeted deletion of both alleles of the ptger2 encoding the EP2 receptor were originally generated by Dr Richard Breyer (Vanderbilt...

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Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 restrains macrophage maturation via E prostanoid receptor 2/protein kinase A signaling

Zasłona

Serezani

Okunishi

et al. 2012

Blood

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“…36,59 Lenalidomide-attenuated pro-inflammatory cytokines including TNFα, γIFN, IL1β and macrophage inhibitory factor (MIF) have been previously described to interact with master pathways/molecules such as CXCR4-SDF1 axis, collagenases, integrins and eicosanoids in controlling cell migration and mobilization. 60-63 Thus, the immunomodulatory effects exerted by IMiDs seem to influence the BM niche in a way non-del5q/5q AML cells physically detach from BM stroma. Future in vivo imaging studies will precisely define the mechanisms underlying the lenalidomide-mediated AML chemotaxis.…”

Section: Discussionmentioning

confidence: 99%

IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AML

et al. 2018

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Treatment for acute myeloid leukemia (AML) remains suboptimal and many patients remain refractory or relapse upon standard chemotherapy based on nucleoside analogs plus anthracyclines. The crosstalk between AML cells and the BM stroma is a major mechanism underlying therapy resistance in AML. Lenalidomide and pomalidomide, a new generation immunomodulatory drugs (IMiDs), possess pleiotropic anti-leukemic properties including potent immune-modulating effects and are commonly used in hematological malignances associated with intrinsic dysfunctional BM such as myelodysplastic syndromes and multiple myeloma. Whether IMiDs may improve the efficacy of current standard treatment in AML remains understudied. Here, we have exploited in vitro and in vivo preclinical AML models to analyze whether IMiDs potentiate the efficacy of AraC/Idarubicin-based standard AML chemotherapy by interfering with the BM stroma-mediated chemoresistance. We report that IMiDs do not exert cytotoxic effects on either non-del5q/5q- AML cells nor BM-MSCs, but they enhance the immunomodulatory properties of BM-MSCs. When combined with AraC/Idarubicin, IMiDs fail to circumvent BM stroma-mediated resistance of non-del5q/5q- AML cells in vitro and in vivo but induce robust extramedullary mobilization of AML cells. When administered as a single agent, lenalidomide specifically mobilizes non-del5q/5q- AML cells, but not healthy CD34+ cells, to peripheral blood (PB) through specific downregulation of CXCR4 in AML blasts. Global gene expression profiling supports a migratory/mobilization gene signature in lenalidomide-treated non-del5q/5q- AML blasts but not in CD34+ cells. Collectively, IMiDs mobilize non-del5q/5q- AML blasts to PB through CXCR4 downregulation, but fail to potentiate AraC/Idarubicin activity in preclinical models of non-del5q/5q- AML.

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“…PGE2 exhibits a stable and direct hematopoietic regulatory ability (1,11,21–25). PGE2 promotes HSC homing following transplantation and prevents its dysfunction with clinical application prospects.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 promotes human CD34+ cells homing through EP2 and EP4 in vitro

Wang

Lai

Tang

et al. 2017

Molecular Medicine Reports

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Recently, certain studies have demonstrated in vitro that prostaglandin E2 (PGE2) promotes human cluster of differentiation (CD)34+ cell homing. However, the sub-type receptors activated by PGE2 are unknown, as the PGE2 receptor EP1-4 subtypes (EP1-4) are expressed on the membrane of human CD34+ cells. Based on the above, the present study aimed to screen the receptor subtype activity by PGE2 to promote human CD34+ cell homing. It was observed that human CD34+ cells expressed the four PGE2 sub-receptors, particularly EP2 and 4. PGE2 increased EP2 and 4 mRNA expression significantly, while EP1 and 3 mRNA exhibited no significant alteration. PGE2, EP2 agonist (EP2A), and EP4A upregulated C-X-C chemokine receptor 4 mRNA and protein expression in human CD34+ cells, and promoted stromal cell-derived factor 1α (SDF-1α) expression in bone marrow mesenchymal stem cells (BMMSCs). These phenomena were inhibited by the associated receptor antagonists. PGE2, EP2A, and EP4A facilitated human CD34+ cell migration towards SDF-1α and BMMSCs. The results of the present study suggested that PGE2 promoted human CD34+ cell homing through EP2 and 4 receptors in vitro.

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Eicosanoid regulation of hematopoiesis and hematopoietic stem and progenitor trafficking

Cited by 97 publications

References 141 publications

Prostaglandin E2 restrains macrophage maturation via E prostanoid receptor 2/protein kinase A signaling

Prostaglandin E2 restrains macrophage maturation via E prostanoid receptor 2/protein kinase A signaling

IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AML

Prostaglandin E2 promotes human CD34+ cells homing through EP2 and EP4 in vitro

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