Sympathetic stimulation facilitates thrombopoiesis by promoting megakaryocyte adhesion, migration, and proplatelet formation

Chen, Shilei; Du, Changhong; Shen, Mingqiang; Zhao, Gaomei; Xu, Yu; Yang, Kang; Wang, Xinmiao; Li, Fengju; Zeng, Dongfeng; Chen, Fang; Wang, Song; Chen, Mo; Wang, Cheng; He, Ting; Wang, Fengchao; Wang, Aiping; Cheng, Tianmin; Su, Yongping; Zhao, Jinghong

doi:10.1182/blood-2015-07-660746

Cited by 61 publications

(51 citation statements)

References 48 publications

(66 reference statements)

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“…Therefore, the effect of MT3 receptor on MK activities needs to be further evaluated. The influence of MT during thrombopoiesis described in this study is consistent with our previous works in which we showed that some neuroendocrine hormones mainly affect the later stages of thrombopoiesis, where they induce a quick elevation of circulating platelets . This is different from some well‐known thrombopoietic cytokines such as TPO, IL‐3, and GM‐CSF, which mainly act during the early and middle stages of platelet production .…”

Section: Discussionsupporting

confidence: 91%

“…To detect human ploidy, cultured MKs were stained for CD41 + cells and then permeabilized with methanol and labeled with propidium iodide (PI, Invitrogen). CD41 + cells were gated for analysis, as previously described . Platelet production was investigated as reported, and pellets containing MKs and platelets were analyzed after labeling with CD41, CD42b, and PI (BioLegend or Emfret Analytics) after a two‐step centrifugation.…”

Section: Methodsmentioning

confidence: 99%

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Melatonin enhances thrombopoiesis through ERK1/2 and Akt activation orchestrated by dual adaptor for phosphotyrosine and 3‐phosphoinositides

Chen

Wang

et al. 2020

Journal of Pineal Research

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Melatonin (MT), endogenously secreted by the pineal gland, is closely related to multiple biological processes; however, its effect on thrombopoiesis is still not well illustrated. Here, we demonstrate that MT administration can elevate peripheral platelet levels. Analysis of different stages in thrombopoiesis reveals that MT has the capacity to promote the expansion of CD34+ and CD41+ cells, and accelerate proplatelet formation (PPF) and platelet production. Furthermore, in vivo experiments show that MT has a potential therapeutic effect on radiation‐induced thrombocytopenia. The underlying mechanism suggests that both extracellular signal‐regulated kinase 1/2 (ERK1/2) and Akt signaling are involved in the processes of thrombopoiesis facilitated by MT. Interestingly, in addition to the direct regulation of Akt signaling by its upstream phosphoinositide 3‐kinase (PI3K), ERK1/2 signaling is also regulated by PI3K via its effector, dual adaptor for phosphotyrosine and 3‐phosphoinositides (DAPP1), in megakaryocytes after MT treatment. Moreover, the expression level of DAPP1 during megakaryocyte differentiation is closely related to the activation of ERK1/2 and Akt at different stages of thrombopoiesis. In conclusion, our data suggest that MT treatment can promote thrombopoiesis, which is modulated by the DAPP1‐orchestrated activation of ERK1/2 and Akt signaling.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Melatonin enhances thrombopoiesis through ERK1/2 and Akt activation orchestrated by dual adaptor for phosphotyrosine and 3‐phosphoinositides

Chen

Wang

et al. 2020

Journal of Pineal Research

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“…For example, studies under chronic stress showed that release of catecholamines from sympathetic nerves in the bone marrow affects megakaryopoiesis, leading to increased release of platelets into the circulation that are prone to activation in a α2‐AR‐ extracellular signal‐regulated kinase (ERK1/2)‐dependent manner. This enhanced thrombopoiesis of highly reactive platelets was shown to contribute to the aggravation of the atherosclerosis in ApoE‐deficient mice . In a somewhat similar way, sympatho‐adrenergic signalling triggered by a heart attack incites inhibitory effects on the distal bone marrow, through β3‐AR‐dependent adrenergic signalling in hematopoietic niche cells.…”

Section: Adrenergic Signalling During Vascular Inflammationmentioning

confidence: 88%

Neutrophils as effectors of vascular inflammation

Gómez-Moreno

Adrover

Hidalgo

2018

Eur J Clin Investigation

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Vascular inflammation underlies most forms of cardiovascular disease, which remains a prevalent cause of death among the global population. Advances in the biology of neutrophils, as well as insights into their dynamics in tissues, have revealed that these cells are prominent drivers of vascular inflammation though derailed activation within blood vessels. The development of powerful imaging techniques, as well as identification of cells and molecules that regulate their activation within vessels, including platelets and catecholamines, has been instrumental to better understand the mechanisms through which neutrophils protect or damage the organism. Other advances in our understanding of how these leucocytes exert detrimental functions on neighbouring cells, including the formation of DNA-based extracellular traps, constitute milestones in defining neutrophil-driven inflammation. Here, we review emerging mechanisms that regulate intravascular activation and effector functions of neutrophils, and discuss specific pathologies in which these processes are relevant. We argue that identification of pathways and mechanisms specifically engaged within the vasculature may provide effective therapies to treat this prevalent group of pathologies.

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“…The adhesion assay was performed according to previous reports [17]. MKs derived from CD34 + cells were cultured for 11 days and pre-incubated with 2’,7’-bis-(2-carboxyethyl)-5-(-and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF AM, Beyotime, China) for 1 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Effect of radiation-induced endothelial cell injury on platelet regeneration by megakaryocytes

Chen

Shen

Zeng

et al. 2017

Journal of Radiation Research

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Thrombocytopenia is an important cause of hemorrhage and death after radiation injury, but the pathogenesis of radiation-induced thrombocytopenia has not been fully characterized. Here, we investigated the influence of radiation-induced endothelial cell injury on platelet regeneration. We found that human umbilical vein endothelial cells (HUVECs) underwent a high rate of apoptosis, accompanied by a significant reduction in the expression of vascular endothelial growth factor (VEGF) at 96 h after radiation. Subsequent investigations revealed that radiation injury lowered the ability of HUVECs to attract migrating megakaryocytes (MKs). Moreover, the adhesion of MKs to HUVECs was markedly reduced when HUVECs were exposed to radiation, accompanied by a decreased production of platelets by MKs. In vivo study showed that VEGF treatment significantly promoted the migration of MKs into the vascular niche and accelerated platelet recovery in irradiated mice. Our studies demonstrate that endothelial cell injury contributes to the slow recovery of platelets after radiation, which provides a deeper insight into the pathogenesis of thrombocytopenia induced by radiation.

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Sympathetic stimulation facilitates thrombopoiesis by promoting megakaryocyte adhesion, migration, and proplatelet formation

Abstract: Key Points NE and EPI promote megakaryocyte adhesion, migration, and proplatelet formation via α2-adrenoceptor-ERK1/2 signaling. Sympathetic stimulation enhances platelet production, which may facilitate recovery of thrombocytopenia or aggravate atherosclerosis.

Cited by 61 publications

References 48 publications

Melatonin enhances thrombopoiesis through ERK1/2 and Akt activation orchestrated by dual adaptor for phosphotyrosine and 3‐phosphoinositides

Melatonin enhances thrombopoiesis through ERK1/2 and Akt activation orchestrated by dual adaptor for phosphotyrosine and 3‐phosphoinositides

Neutrophils as effectors of vascular inflammation

Effect of radiation-induced endothelial cell injury on platelet regeneration by megakaryocytes

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