TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide

Morad, Hassan; Luqman, Suaib; Tan, Chun-Hsiang; Swann, Victoria; McNaughton, Peter A.

doi:10.1038/s41598-021-88224-5

Cited by 19 publications

(16 citation statements)

References 58 publications

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“…MCP1 secreted by endothelial cells in response to subendothelial deposition of oxLDL is one of the initial driving forces of macrophage infiltration during atherosclerosis [112]. Similar to our findings, hydrogen peroxide (H 2 O 2 ) was shown to attract neutrophil migration both in vivo and in intro, which was also abolished by TRPM2 knockout or TRPM2 inhibition [114]. H 2 O 2 is an important molecular signal generated during inflammation [115].…”

Section: Trpm2 In Atherosclerosissupporting

confidence: 84%

A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death

Zong

Lin

Feng

et al. 2022

Cells

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Ischemic stroke causes a heavy health burden worldwide, with over 10 million new cases every year. Despite the high prevalence and mortality rate of ischemic stroke, the underlying molecular mechanisms for the common etiological factors of ischemic stroke and ischemic stroke itself remain unclear, which results in insufficient preventive strategies and ineffective treatments for this devastating disease. In this review, we demonstrate that transient receptor potential cation channel, subfamily M, member 2 (TRPM2), a non-selective ion channel activated by oxidative stress, is actively involved in all the important steps in the etiology and pathology of ischemic stroke. TRPM2 could be a promising target in screening more effective prophylactic strategies and therapeutic medications for ischemic stroke.

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Section: Trpm2 In Atherosclerosissupporting

confidence: 84%

A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death

Zong

Lin

Feng

et al. 2022

Cells

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“…Different reports have shown that these channels can enhance T cell receptor stimulation in T cells and inhibit reactive oxygen species production in phagocytic cells (Di et al, 2011;Chung et al, 2015;Syed Mortadza et al, 2015;Morad et al, 2021). Furthermore, this channel can promote the secretion of cytokines such as IL-2, IL-17, and IFN-γ (Melzer et al, 2012).…”

Section: Calcium Channelsmentioning

confidence: 99%

Modulation of Adaptive Immunity and Viral Infections by Ion Channels

et al. 2021

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Most cellular functions require of ion homeostasis and ion movement. Among others, ion channels play a crucial role in controlling the homeostasis of anions and cations concentration between the extracellular and intracellular compartments. Calcium (Ca2+) is one of the most relevant ions involved in regulating critical functions of immune cells, allowing the appropriate development of immune cell responses against pathogens and tumor cells. Due to the importance of Ca2+ in inducing the immune response, some viruses have evolved mechanisms to modulate intracellular Ca2+ concentrations and the mobilization of this cation through Ca2+ channels to increase their infectivity and to evade the immune system using different mechanisms. For instance, some viral infections require the influx of Ca2+ through ionic channels as a first step to enter the cell, as well as their replication and budding. Moreover, through the expression of viral proteins on the surface of infected cells, Ca2+ channels function can be altered, enhancing the pathogen evasion of the adaptive immune response. In this article, we review those ion channels and ion transporters that are essential for the function of immune cells. Specifically, cation channels and Ca2+ channels in the context of viral infections and their contribution to the modulation of adaptive immune responses.

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“…with H 2 O 2 or LPS and at experimental time points (see methods below), mice were euthanised by cervical dislocation. The peritoneal lavage was recovered as above, and samples of the suspensions were immediately spun down onto glass slides using a cytocentrifuge (Sigma 2-7 Cyto, Shandon TM , Germany as described below) and leukocytes (neutrophils, macrophages) identi ed through a fast-acting modi ed version of the May-Grünwald-Giemsa staining and subsequent cell type identi cation as shown in Morad et al 2021. The remaining cell suspension was then centrifuged for 10 min at 200 RCF and supernatants were collected and frozen at -20 o C for cyto/chemokine analysis by ELISA and cf-DNA(NET) quanti cation using Quant-iT™ PicoGreen kit (Thermo Fisher).…”

Section: In Vivo Peritoneal Chemotaxis Experimentsmentioning

confidence: 99%

“…Samples of the BAL uid were immediately spun down onto glass slides using a cytocentrifuge (as described below) and neutrophils identi ed through a fast-acting modi ed version of the May-Grünwald-Giemsa staining and subsequent cell type identi cation as shown in Morad et al 2021. The remaining cell suspensions was then centrifuged for 10 min at 200 RCF and supernatants were collected and frozen at -20°C for cyto/chemokine analysis by ELISA and cf-DNA (NET) quanti cation using Quant-iT™ PicoGreen kit (Thermo Fisher).…”

Section: Isolation Of Mouse Balf Neutrophilsmentioning

confidence: 99%

Artemisinin inhibits innate immune cell chemotaxis, cytokine production and NET release

Morad

Luqman

Pinto

et al. 2022

Preprint

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Immune cell chemotaxis to the sites of pathogen invasion is critical for fighting infection, but in life-threatening conditions such as sepsis and Covid-19, excess activation of the innate immune system is thought to cause a damaging invasion of immune cells into tissues and a consequent excessive release of cytokines. In these circumstances, tempering excessive activation of the innate immune system may, paradoxically, promote recovery. Here we identify the antimalarial compound artemisinin as a potent and selective inhibitor of neutrophil and macrophage chemotaxis induced by many chemotactic agents. Artemisinin released calcium from intracellular stores in a similar way to thapsigargin, a known inhibitor of the Sarco/Endoplasmic Reticulum Calcium ATPase pump (SERCA), but unlike thapsigargin, artemisinin blocks only the SERCA3 isoform. Inhibition of SERCA3 by artemisinin was irreversible and was inhibited by iron chelation, suggesting iron-catalysed alkylation of a specific cysteine residue in SERCA3 as the mechanism by which artemisinin inhibits immune cell motility. In murine infection models, artemisinin potently suppressed immune cell invasion into both peritoneum and lung in vivo and inhibited the release of cytokines/chemokines and neutrophil extracellular traps (NETs). This work suggests that artemisinin may have value as a therapy in conditions such as sepsis and Covid-19 in which over-activation of the innate immune system causes tissue injury that can lead to death.

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TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide

Cited by 19 publications

References 58 publications

A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death

A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death

Modulation of Adaptive Immunity and Viral Infections by Ion Channels

Artemisinin inhibits innate immune cell chemotaxis, cytokine production and NET release

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