STIM1 calcium sensor is required for activation of the phagocyte oxidase during inflammation and host defense

Zhang, Hong; Clemens, Regina A.; Liu, Fengchun; Hu, Yongmei; Baba, Yoshifumi; Theodore, Pierre; Kurosaki, Tomohiro; Lowell, Clifford A.

doi:10.1182/blood-2012-08-450403

Cited by 75 publications

(98 citation statements)

References 56 publications

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“…Recent studies revealed that neutrophil NOX2 is important for the activities of phosphatase and tensin homolog (PTEN) and AKT 47 and that SOCE activates PKCa/b, thereby phosphorylating p47 phox during neutrophil activation. 30 However, we found that PTEN activity is reduced in both NOX2 KO platelets and neutrophils after agonist stimulation (supplemental Figure 6) and that there is no difference in PKCa/b phosphorylation between WT and NOX2 KO cells after agonist stimulation or TG-induced SOCE (supplemental Figure 7). Thus, consistent with our recent report demonstrating the importance of AKT2 in Ca 21 signaling during neutrophil activation, 1 these findings provide evidence that AKT signaling regulates ROS-mediated Ca 21 signaling.…”

Section: Discussionmentioning

confidence: 76%

“…30 However, it remains poorly understood whether NOX2 deletion affects Ca 21 mobilization, which is critical for regulating the function of cell surface receptors. 31 We found that compared with WT platelets, NOX2 KO platelets significantly inhibited intracellular Ca 21 release upon thrombin stimulation ( Figure 6A) but did not alter SOCE in the presence of 2 mM CaCl 2 .…”

Section: Platelet and Neutrophil Nox2 Differentially Modulate Ca 21 Mmentioning

confidence: 99%

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NOX2 is critical for heterotypic neutrophil-platelet interactions during vascular inflammation

Kim¹,

Li²,

Tseng

et al. 2015

Blood

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Key Points• NOX2-generated ROS regulate the function of surface receptors required for platelet-neutrophil interactions during vascular inflammation.Platelet-leukocyte interactions on activated endothelial cells play an important role during microvascular occlusion under oxidative stress conditions. However, it remains poorly understood how neutrophil-platelet interactions are regulated during vascular inflammation. By using intravital microscopy with mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and their bone marrow chimera, we demonstrated that NOX2 from both hematopoietic and endothelial cells is crucial for neutrophil-platelet interactions during tumor necrosis factor alpha-induced venular inflammation. Platelet NOX2-produced reactive oxygen species (ROS) regulated P-selectin exposure upon agonist stimulation and the ligand-binding function of glycoprotein Iba. Furthermore, neutrophil NOX2-generated ROS enhanced the activation and ligand-binding activity of aMb2 integrin following N-formyl-methionyl-leucyl phenylalanine stimulation. Studies with isolated cells and a mouse model of hepatic ischemia/reperfusion injury revealed that NOX2 from both platelets and neutrophils is required for cell-cell interactions, which contribute to the pathology of hepatic ischemia/reperfusion injury. Platelet NOX2 modulated intracellular Ca 21 release but not store-operated Ca 21 entry (SOCE), whereas neutrophil NOX2 was crucial for SOCE but not intracellular Ca 21 release. Different regulation of Ca 21 signaling by platelet and neutrophil NOX2 correlated with differences in the phosphorylation of AKT, ERK, and p38MAPK. Our results indicate that platelet and neutrophil NOX2-produced ROS are critical for the function of surface receptors essential for neutrophil-platelet interactions during vascular inflammation. (Blood. 2015;126(16):1952-1964

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Section: Discussionmentioning

confidence: 76%

Section: Platelet and Neutrophil Nox2 Differentially Modulate Ca 21 Mmentioning

confidence: 99%

NOX2 is critical for heterotypic neutrophil-platelet interactions during vascular inflammation

Kim¹,

Li²,

Tseng

et al. 2015

Blood

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“…A previous study demonstrated in an in vivo experiment that STIM1 in neutrophils plays a role in bacterial clearance and is involved in ischemia-reperfusion injury. 5 However, several studies demonstrated differential roles for STIM1 and/or STIM2 depending on the immune cell type. The relative expression levels of both molecules are cell type dependent, indicating distinct functions.…”

mentioning

confidence: 99%

STIMulation of signaling in neutrophils

Stadtmann

Zarbock

2017

Blood

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“…In particular, TRPC1 is reportedly associated with cell proliferation, cell migration, enzyme and fluid secretion, normal metabolism in various organ systems, and cancer metastasis (6,10,11). TRPC1 could also form a heteromultimer with Orai1 and stromal interaction molecule 1 (STIM1), which are essential for Ca 2ϩ signaling (12)(13)(14). This interaction may allow the activation of immune ligands (e.g., Toll-like receptors [TLRs]), and thus TRPC channel proteins may play a role in host defense, which has been demonstrated only in the context of lipopolysaccharide (LPS) by regulating cytokine production and inflammatory response.…”

mentioning

confidence: 99%

Transient Receptor Potential Channel 1 Deficiency Impairs Host Defense and Proinflammatory Responses to Bacterial Infection by Regulating Protein Kinase Cα Signaling

Zhou

Yan

Sun

et al. 2015

Molecular and Cellular Biology

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dTransient receptor potential channel 1 (TRPC1) is a nonselective cation channel that is required for Ca 2؉ homeostasis necessary for cellular functions. However, whether TRPC1 is involved in infectious disease remains unknown. Here, we report a novel function for TRPC1 in host defense against Gram-negative bacteria. TRPC1؊/؊ mice exhibited decreased survival, severe lung injury, and systemic bacterial dissemination upon infection. Furthermore, silencing of TRPC1 showed decreased Ca 2؉ entry, reduced proinflammatory cytokines, and lowered bacterial clearance. Importantly, TRPC1 functioned as an endogenous Ca 2؉ entry channel critical for proinflammatory cytokine production in both alveolar macrophages and epithelial cells. We further identified that bacterium-mediated activation of TRPC1 was dependent on Toll-like receptor 4 (TLR4), which induced endoplasmic reticulum (ER) store depletion. After activation of phospholipase C␥ (PLC-␥), TRPC1 mediated Ca 2؉ entry and triggered protein kinase C␣ (PKC␣) activity to facilitate nuclear translocation of NF-B/Jun N-terminal protein kinase (JNK) and augment the proinflammatory response, leading to tissue damage and eventually mortality. These findings reveal that TRPC1 is required for host defense against bacterial infections through the TLR4-TRPC1-PKC␣ signaling circuit. P seudomonas aeruginosa and Klebsiella pneumoniae are opportunistic Gram-negative bacteria that infect a broad range of individuals, particularly immunocompromised people, causing high morbidity and mortality. These bacteria are increasingly becoming resistant to almost all the conventional antibiotics and remain major health threats (1, 2). Better understanding of the mechanism of host-pathogen interaction may facilitate the development of novel approaches to treat these infections. A number of studies have thus far focused on the pathogenesis of P. aeruginosa and K. pneumoniae in airway infectious diseases and have identified some critical innate immunity regulators for early-stage host defense (3-5).Members of the transient receptor potential channel (TRPC) and Orai families have been suggested as mediators of Ca 2ϩ entry channels in nonexcitable cells (6). Activation of the phospholipase C (PLC) signaling pathway generates inositol trisphosphate (IP 3 ) and diacylglycerol (DAG), which initiates Ca 2ϩ release from the endoplasmic reticulum (ER) stores followed by the activation of Ca 2ϩ entry channels that increase cytosolic Ca 2ϩ levels (7, 8). Ca 2ϩ entry through receptor-mediated channels is essential for regulating cellular functions, and TRPC1, which functions as a nonselective cation channel in many cell types, has been shown to be important in Ca 2ϩ entry that is initiated by store depletion (7, 9). In particular, TRPC1 is reportedly associated with cell proliferation, cell migration, enzyme and fluid secretion, normal metabolism in various organ systems, and cancer metastasis (6, 10, 11). TRPC1 could also form a heteromultimer with Orai1 and stromal interaction molecule 1 (STIM1), which are e...

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STIM1 calcium sensor is required for activation of the phagocyte oxidase during inflammation and host defense

Abstract: Key Points STIM1-mediated calcium entry is critical for neutrophil superoxide release via activation of calcium-sensitive PKCα and PKCβ. STIM1 deficiency results in profound susceptibility to bacterial infection, but also protection in hepatic ischemia/reperfusion injury.

Cited by 75 publications

References 56 publications

NOX2 is critical for heterotypic neutrophil-platelet interactions during vascular inflammation

NOX2 is critical for heterotypic neutrophil-platelet interactions during vascular inflammation

STIMulation of signaling in neutrophils

Transient Receptor Potential Channel 1 Deficiency Impairs Host Defense and Proinflammatory Responses to Bacterial Infection by Regulating Protein Kinase Cα Signaling

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