Endocannabinoids Are Expressed in Bone Marrow Stromal Niches and Play a Role in Interactions of Hematopoietic Stem and Progenitor Cells with the Bone Marrow Microenvironment

Jiang, Shuxian; Zagożdżon, Radosław; Alberich-Jordà, Meritxell; Parmar, Kalindi; Fu, Yue; Williams, Josh; Wood, Jeff T.; Makriyannis, Alexandros; Banu, Naheed; Avraham, Shalom; Groopman, Jerome E.; Avraham, Hava

doi:10.1074/jbc.m110.144758

Cited by 15 publications

(11 citation statements)

References 43 publications

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“…CB 2 R may also function as a chemotactic modulator, as CB 2 R activation inhibits CXCR4-induced chemotaxis in transformed lymphocytes [16] . CB 2 R has further been shown to regulate lymphocyte egress from the bone marrow in a role previously attributed largely to CXCR4 [17] , [18] . These findings suggest that CB 2 R may play a role in regulating chemokine receptor signaling, specifically the activity of CXCR4.…”

Section: Introductionmentioning

confidence: 97%

Cannabinoid Receptor 2-Mediated Attenuation of CXCR4-Tropic HIV Infection in Primary CD4+ T Cells

et al. 2012

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Agents that activate cannabinoid receptor pathways have been tested as treatments for cachexia, nausea or neuropathic pain in HIV-1/AIDS patients. The cannabinoid receptors (CB 1 R and CB 2 R) and the HIV-1 co-receptors, CCR5 and CXCR4, all signal via Gαi-coupled pathways. We hypothesized that drugs targeting cannabinoid receptors modulate chemokine co-receptor function and regulate HIV-1 infectivity. We found that agonism of CB 2 R, but not CB 1 R, reduced infection in primary CD4+ T cells following cell-free and cell-to-cell transmission of CXCR4-tropic virus. As this change in viral permissiveness was most pronounced in unstimulated T cells, we investigated the effect of CB 2 R agonism on to CXCR4-induced signaling following binding of chemokine or virus to the co-receptor. We found that CB 2 R agonism decreased CXCR4-activation mediated G-protein activity and MAPK phosphorylation. Furthermore, CB 2 R agonism altered the cytoskeletal architecture of resting CD4+ T cells by decreasing F-actin levels. Our findings suggest that CB 2 R activation in CD4+ T cells can inhibit actin reorganization and impair productive infection following cell-free or cell-associated viral acquisition of CXCR4-tropic HIV-1 in resting cells. Therefore, the clinical use of CB 2 R agonists in the treatment of AIDS symptoms may also exert beneficial adjunctive antiviral effects against CXCR4-tropic viruses in late stages of HIV-1 infection.

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Section: Introductionmentioning

confidence: 97%

Cannabinoid Receptor 2-Mediated Attenuation of CXCR4-Tropic HIV Infection in Primary CD4+ T Cells

et al. 2012

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“…We also showed that agonism of cannabinoid receptors, receptors for the eicosanoid-related endocannabinoids, act in an opposing fashion to PGE 2 signaling, decreasing adhesion molecule expression and CXCR4, and enhancing G-CSF mobilization [104**]. Two separate reports by Jiang et al have also demonstrated that cannabinoid signaling mediates mobilization, and that endocannabinoids are expressed in bone marrow and increase HPC migration and proliferation in vitro [105**,106*]. Another report demonstrated that cannabinoids mobilize myeloid-derived suppressor cells, with a possible role for endogenous G-CSF production [107*].…”

Section: Fatty Acids For the Futurementioning

confidence: 99%

Many mechanisms mediating mobilization: an alliterative review

Hoggatt

Pelus

2011

Current Opinion in Hematology

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Purpose of review Blood cell production is maintained by hematopoietic stem cells (HSC) that reside in specialized niches within bone marrow. Treatment with granulocyte-colony stimulating factor (G-CSF) causes HSC egress from bone marrow niches and trafficking to the peripheral blood, a process termed “mobilization”. Although the mobilization phenomenon has been known for some time and is utilized clinically to acquire HSC for transplant, the mechanisms mediating HSC release are not completely understood. We discuss recent advances and controversies in defining mechanisms responsible for G-CSF induced mobilization. Recent findings New reports define a role for resident monocytes/macrophages in maintaining niche cells, which is diminished after G-CSF treatment, suggesting a new mechanism for mobilization. While osteoblasts have been reported to be a primary component of the HSC niche, new results suggest a unique niche composed of innervated mesenchymal stem cells. Modulating bioactive lipid signaling also facilitates mobilization, and may define a future therapeutic strategy. Summary Hematopoietic mobilization by G-CSF is primarily mediated by alterations to the bone marrow niche by both direct and indirect mechanisms, rather than directly altering HSC function. Further understanding of the processes mediating mobilization will advance our understanding on the cellular and molecular components of the HSC niche.

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“…In a further series of studies, we found that single administration of the CB 2 selective agonist GP1a and the dual CB 1 /CB 2 agonist CP55940 but not the CB 1 selective agonist ACEA significantly mobilized hematopoietic progenitor cells to the peripheral blood and that the addition of a single dose of CP55940 to a standard 4-day mobilizing regimen of G-CSF significantly increased progenitor cell mobilization compared to G-CSF alone [110]. Two separate reports by Jiang et al have also now demonstrated that cannabinoid signaling mediates mobilization, and that endocannabinoids are expressed in bone marrow and increase HPC migration and proliferation in vitro [117,118]. …”

Section: The Yin and Yang Of Prostaglandins And Endocannabinoids In Hmentioning

confidence: 99%

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

Pelus

Hoggatt

2011

Prostaglandins & Other Lipid Mediators

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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.

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Endocannabinoids Are Expressed in Bone Marrow Stromal Niches and Play a Role in Interactions of Hematopoietic Stem and Progenitor Cells with the Bone Marrow Microenvironment

Cited by 15 publications

References 43 publications

Cannabinoid Receptor 2-Mediated Attenuation of CXCR4-Tropic HIV Infection in Primary CD4+ T Cells

Cannabinoid Receptor 2-Mediated Attenuation of CXCR4-Tropic HIV Infection in Primary CD4+ T Cells

Many mechanisms mediating mobilization: an alliterative review

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

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