Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury

Chou, Wen Hai; Choi, Doo Sup; Zhang, Hong; Mu, Dezhi; McMahon, Tom; Kharazia, Viktor; Lowell, Clifford A.; Ferriero, Donna M.; Messing, Robert O.

doi:10.1172/jci21655

Cited by 82 publications

(74 citation statements)

References 55 publications

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“…PKC-a was further implicated in fMLP-and PMA-induced superoxide generation based on siRNA evidence in HL-60 cells differentiated to resemble granulocytes (Korchak et al 2007). Brown et al (2003) substantiated the role of PKC-d in NADPH oxidase activation and superoxide generation in neutrophils after stimulation with PMA, and Chou et al (2004) showed a marked decrease of TNF-a-induced superoxide production in PKC-d gene deficient neutrophils.…”

Section: Oxidative Burstmentioning

confidence: 62%

“…As described in the previous section, reduced adhesion of PKC-d gene deficient neutrophils after GPCR ligand activation in vitro could be caused by defective signaling downstream of integrin engagement (Chou et al 2004). Evidence for the involvement of PKC isoforms in integrin-dependent outside-in signaling comes from platelets, in which fibrinogen binding causes spreading via outside-in signaling downstream of adhesion via the platelet integrin a IIb b 3 .…”

Section: Adhesion Strengthening and Crawlingmentioning

confidence: 87%

“…In monocytes, Mac-1, but not LFA-1 clustering was shown to result in phosphorylation and activation of PKC-d in a Src kinase dependent manner (Xue et al 2010). Possibly, the reduced static adhesion of PKC-d gene deficient neutrophils (Chou et al 2004) is a consequence of defective signaling downstream of Mac-1 clustering, as well. In addition to spreading and adhesion strengthening, PKC isoforms were implicated in integrindependent events that are mediated by outside-in signaling, such as superoxide generation and neutrophil degranulation (see next sections).…”

Section: Adhesion Strengthening and Crawlingmentioning

confidence: 99%

“…Exp. (2011) 59:79-87 81 with fMLP or IL-8, PKC-d gene deficient neutrophils showed markedly reduced adhesion to plates coated with fetal calf serum in comparison to wild type neutrophils (Chou et al 2004). This type of ''static'' adhesion assay cannot distinguish whether PKC-d is involved in inside-out signaling triggering integrin conformational change or in post-adhesion events such as cell spreading and integrin outside-in signaling.…”

Section: Chemokine Receptor Signaling Can Induce Neutrophil Arrest Anmentioning

confidence: 99%

“…In addition to defective adhesion and superoxide generation, PKC-d gene deficient neutrophil showed markedly reduced lactoferrin degranulation following stimulation with fMLP or PMA (Chou et al 2004). Popa-Nita et al (2009) implicated PKC isoforms in urate crystal-induced activation and degranulation of neutrophils, which play a crucial role in gouty inflammation.…”

Section: Degranulationmentioning

confidence: 99%

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Protein Kinase C Isoforms in Neutrophil Adhesion and Activation

Bertram

Ley

2011

Arch. Immunol. Ther. Exp.

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Neutrophils are the first line of defense against bacterial and mycotic pathogens. In order to reach the pathogens, neutrophils need to transmigrate through the vascular endothelium and migrate to the site of infection. Defense strategies against pathogens include phagocytosis, production and release of oxygen radicals through the oxidative burst, and degranulation of antimicrobial and inflammatory molecules. Protein kinase C (PKC)-δ is required for full assembly of NADPH oxidase and activation of the respiratory burst. Neutrophils also express PKC-α and -β, which may be involved in adhesion, degranulation and phagocytosis, but the evidence is not conclusive yet. This review focuses on the potential impact of protein kinase C isoforms on neutrophil adhesion and activation.

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Section: Oxidative Burstmentioning

confidence: 62%

Section: Adhesion Strengthening and Crawlingmentioning

confidence: 87%

Section: Adhesion Strengthening and Crawlingmentioning

confidence: 99%

Section: Chemokine Receptor Signaling Can Induce Neutrophil Arrest Anmentioning

confidence: 99%

Section: Degranulationmentioning

confidence: 99%

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Protein Kinase C Isoforms in Neutrophil Adhesion and Activation

Bertram

Ley

2011

Arch. Immunol. Ther. Exp.

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Significance of marrow‐derived nicotinamide adenine dinucleotide phosphate oxidase in experimental ischemic stroke

Tang

Zheng

Giffard

et al. 2011

Annals of Neurology

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Objective Reperfusion after stroke leads to infiltration of inflammatory cells into the ischemic brain. NADPH oxidase (NOX2) is a major enzyme system which generates superoxide in immune cells. We studied the effect of NOX2 derived from the immune cells in the brain and in blood cells in experimental stroke. Methods To establish whether NOX2 plays a role in brain ischemia, strokes were created in mice, then mice were treated with the NOX2 inhibitor, apocynin or vehicle and compared to mice deficient in NOX2's gp91 subunit and their wildtype littermates. To determine whether NOX2 in circulating cells versus brain resident cells contribute to ischemic injury, bone marrow chimeras were generated by transplanting bone marrow from wildtype or NOX2 deficient mice into NOX2 or wildtype hosts, respectively. Results Apocynin and NOX2 deletion both significantly reduced infarct size, blood-brain barrier disruption and hemorrhagic transformation of the infarcts, compared to untreated wildtype controls. This was associated with decreased MMP-9 expression and reduced loss of tight junction proteins. NOX2 deficient mice receiving wildtype marrow had better outcomes compared to the wildtype mice receiving wildtype marrow. Interestingly, wildtype mice receiving NOX2 deficient marrow had even smaller infarct sizes and less hemorrhage than NOX2 deficient mice receiving wildtype marrow. Interpretation This indicates that NOX2, whether present in circulating cells or brain resident cells, contributes to ischemic brain injury and hemorrhage. However, NOX2 from the circulating cells contributed more to the exacerbation of stroke than that from brain resident cells. These data suggest the importance of targeting the peripheral immune system for treatment of stroke.

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Ischemia/Reperfusion

Kalogeris

Baines

Krenz

et al. 2016

Comprehensive Physiology

626

565

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Ischemic disorders, such as myocardial infarction, stroke, and peripheral vascular disease, are the most common causes of debilitating disease and death in westernized cultures. The extent of tissue injury relates directly to the extent of blood flow reduction and to the length of the ischemic period, which influence the levels to which cellular ATP and intracellular pH are reduced. By impairing ATPase-dependent ion transport, ischemia causes intracellular and mitochondrial calcium levels to increase (calcium overload). Cell volume regulatory mechanisms are also disrupted by the lack of ATP, which can induce lysis of organelle and plasma membranes. Reperfusion, although required to salvage oxygen-starved tissues, produces paradoxical tissue responses that fuel the production of reactive oxygen species (oxygen paradox), sequestration of proinflammatory immunocytes in ischemic tissues, endoplasmic reticulum stress, and development of postischemic capillary no-reflow, which amplify tissue injury. These pathologic events culminate in opening of mitochondrial permeability transition pores as a common end-effector of ischemia/reperfusion (I/R)-induced cell lysis and death. Emerging concepts include the influence of the intestinal microbiome, fetal programming, epigenetic changes, and microparticles in the pathogenesis of I/R. The overall goal of this review is to describe these and other mechanisms that contribute to I/R injury. Because so many different deleterious events participate in I/R, it is clear that therapeutic approaches will be effective only when multiple pathologic processes are targeted. In addition, the translational significance of I/R research will be enhanced by much wider use of animal models that incorporate the complicating effects of risk factors for cardiovascular disease.

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Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury

Cited by 82 publications

References 55 publications

Protein Kinase C Isoforms in Neutrophil Adhesion and Activation

Protein Kinase C Isoforms in Neutrophil Adhesion and Activation

Significance of marrow‐derived nicotinamide adenine dinucleotide phosphate oxidase in experimental ischemic stroke

Ischemia/Reperfusion

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