Novel evidence that the P2X1 purinergic receptor–Nlrp3 inflammasome axis orchestrates optimal trafficking of hematopoietic stem progenitors cells

Bujko, Kamila; Adamiak, Mateusz; Abdelbaset‐Ismail, Ahmed; Ilowska, Nicoletta; Ratajczak, Janina; Kucia, Magdalena; Ratajczak, Mariusz Z.

doi:10.5603/fhc.a2022.0027

Cited by 7 publications

(9 citation statements)

References 39 publications

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“…All these antibodies were purchased from BD Biosciences. After 30 min of staining, the cells were washed, resuspended, and sorted using a Moflo XDP cell sorter (Beckman Coulter, Indianapolis, IN, USA) as populations of SKL (Sca-1 + c-Kit + Lin − ) cells [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

The Nox2-ROS-Nlrp3 Inflammasome Signaling Stimulates in the Hematopoietic Stem/Progenitor Cells Lipogenesis to Facilitate Membrane Lipid Raft Formation

Abdelbaset‐Ismail

Ciechanowicz

Bujko

et al. 2022

Stem Cell Rev and Rep

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Proliferation, metabolism, and migration of hematopoietic stem/progenitor cells (HSPCs) are coordinated by receptors expressed on outer cell membranes that are integrated into microdomains, known as membrane lipid rafts (MLRs). These structures float freely in the cell membrane bilayer and are enriched in cholesterol and sphingolipids for their functional integrity. Receptors, if expressed in MLRs, have prolonged occupancy on the cell surface and enhanced signaling power. Based on this, we have become interested in the regulation of synthesis of MLRs components in HSPCs. To address this, we tested the effect of selected factors that promote proliferation or migration and their potential involvement in the synthesis of MLRs components in HSPCs. Based on our previous research showing that HSPCs from Nox2-KO and Nlrp3-KO mice display a profound defect in MLRs formation, we focused on the role of Nox2-ROS-Nlrp3 inflammasome in regulating lipogenesis in HSPCs. We found that while at steady state conditions, Nox2-derived ROS is required for a proper expression of enzymes regulating lipogenesis, during inflammation, this effect is augmented by Nlrp3 inflammasome. Thus, our data sheds new light on the regulation of lipogenesis in HSPCs and the involvement of the Nox2-ROS-Nlrp3 inflammasome axis that differently regulates lipogenesis at steady state conditions and in response to inflammation, modulating MLRs-mediated responsiveness of these cells to external stimuli. Graphical Abstract

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Section: Methodsmentioning

confidence: 99%

The Nox2-ROS-Nlrp3 Inflammasome Signaling Stimulates in the Hematopoietic Stem/Progenitor Cells Lipogenesis to Facilitate Membrane Lipid Raft Formation

Abdelbaset‐Ismail

Ciechanowicz

Bujko

et al. 2022

Stem Cell Rev and Rep

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“…The role of purinergic signaling in normal hematopoiesis was the subject of some previous studies [ 30 , 32 , 33 ]. Our group, however, became interested in the role of purinergic signaling in the trafficking of HSPCs as occurs during pharmacological mobilization [ 34 , 35 ], homing, and their engraftment after transplantation [ 36 – 39 ]. To address this issue first, we phenotyped normal human CD34 + and murine Sca-1 + lin − CD45 + cells enriched for HSPCs for expression of the purinergic receptors and CD39 and CD73 ectonucleotidases involved in the enzymatic conversion of eATP to eAdo [ 28 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

“…In our subsequent functional studies, we focused on P2X ionotropic receptors activated exclusively by eATP expressed on both human and murine HSPCs [ 28 , 34 , 36 , 37 , 40 ]. Since these receptors are structurally related and expressed simultaneously, we expected to see some potential functional redundancy characteristic of evolutionary old regulatory pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Since these receptors are structurally related and expressed simultaneously, we expected to see some potential functional redundancy characteristic of evolutionary old regulatory pathways. We began our work with those P2X receptors that are most abundant on murine HSPCs and employed available P2X4-KO and P2X7-KO animals and, in the case of P2X1 and P2X3 specific receptor inhibitors [ 28 , 34 , 36 , 37 , 40 ]. We refrained from studying P2X2, P2X5, and P2X6 members, as these receptors have been dammed to be less involved in normal hematopoiesis [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…We refrained from studying P2X2, P2X5, and P2X6 members, as these receptors have been dammed to be less involved in normal hematopoiesis [ 20 ]. We learned that the absence of functional P2X1, P2X3, P2X4, and P2X7 receptors on murine and human HSPC resulted in their defective chemotactic Transwell migration to major BM-homing chemoattractants, including α-chemokine stromal-derived factor-1 (SDF-1), bioactive phosphosphingolipid—sphingosine-1 phosphate (S1P), and eATP [ 28 , 34 , 36 , 37 , 40 ]. The outcome of these assays indicated that P2X receptors may modulate the HSPCs trafficking as seen in pharmacological mobilization and their homing and engraftment in bone marrow (BM) after transplantation.…”

Section: Introductionmentioning

confidence: 99%

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Hematopoiesis Revolves Around the Primordial Evolutional Rhythm of Purinergic Signaling and Innate Immunity – A Journey to the Developmental Roots

Ratajczak,

Bujko,

Brzezniakiewicz-Janus

et al. 2024

Stem Cell Rev and Rep

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A cell's most significant existential task is to survive by ensuring proper metabolism, avoiding harmful stimuli, and adapting to changing environments. It explains why early evolutionary primordial signals and pathways remained active and regulate cell and tissue integrity. This requires energy supply and a balanced redox state. To meet these requirements, the universal intracellular energy transporter purine nucleotide-adenosine triphosphate (ATP) became an important signaling molecule and precursor of purinergic signaling after being released into extracellular space. Similarly, ancient proteins involved in intracellular metabolism gave rise to the third protein component (C3) of the complement cascade (ComC), a soluble arm of innate immunity. These pathways induce cytosol reactive oxygen (ROS) and reactive nitrogen species (RNS) that regulate the redox state of the cells. While low levels of ROS and RNS promote cell growth and differentiation, supra-physiological concentrations can lead to cell damage by pyroptosis. This balance explains the impact of purinergic signaling and innate immunity on cell metabolism, organogenesis, and tissue development. Subsequently, along with evolution, new regulatory cues emerge in the form of growth factors, cytokines, chemokines, and bioactive lipids. However, their expression is still modulated by both primordial signaling pathways. This review will focus on the data that purinergic signaling and innate immunity carry on their ancient developmental task in hematopoiesis and specification of hematopoietic stem/progenitor cells (HSPCs). Moreover, recent evidence shows both these regulatory pathways operate in a paracrine manner and inside HSPCs at the autocrine level. Graphical Abstract

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Hematopoietic stem cells on the crossroad between purinergic signaling and innate immunity

Franczak

Ulrich

Ratajczak

2023

Purinergic Signalling

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Hematopoiesis is regulated by several mediators such as peptide-based growth factors, cytokines, and chemokines, whose biological effects have been studied for many years. However, several other mediators have been identified recently that affect the fate of hematopoietic stem/progenitor cells (HSPC) as well as non-hematopoietic cells in the bone marrow microenvironment. These new mediators comprise members of purinergic signaling pathways and are active mediators of the soluble arm of innate immunity, the complement cascade (ComC). In this review, we will discuss the coordinated effects of these pathways in regulating the biology of HSPC. Importantly, both purinergic signaling and the ComC are activated in stress situations and interact with specific receptors expressed on HSPC. Evidence has accumulated indicating that some of the purinergic as well as ComC receptors could also be activated intracellularly by intrinsically expressed ligands. To support this recent evidence, our work indicates that the major mediator of purinergic signaling, adenosine triphosphate, and the cleavage product of the fifth component of the ComC (C5), C5a anaphylatoxin, can activate their corresponding receptors expressed on the outer mitochondrial membrane in an autocrine manner. We will also discuss recent evidence that these responses, mediated by purinergic signaling and the ComC network, are coordinated by activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 - reactive oxygen species - NLR family pyrin domain containing 3 (NLRP3) inflammasome (Nox2-ROS-NLRP3) axis.

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Novel evidence that the P2X1 purinergic receptor–Nlrp3 inflammasome axis orchestrates optimal trafficking of hematopoietic stem progenitors cells

Cited by 7 publications

References 39 publications

The Nox2-ROS-Nlrp3 Inflammasome Signaling Stimulates in the Hematopoietic Stem/Progenitor Cells Lipogenesis to Facilitate Membrane Lipid Raft Formation

The Nox2-ROS-Nlrp3 Inflammasome Signaling Stimulates in the Hematopoietic Stem/Progenitor Cells Lipogenesis to Facilitate Membrane Lipid Raft Formation

Hematopoiesis Revolves Around the Primordial Evolutional Rhythm of Purinergic Signaling and Innate Immunity – A Journey to the Developmental Roots

Hematopoietic stem cells on the crossroad between purinergic signaling and innate immunity

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