The molecular regulation of programmed necrotic cell injury

Moquin, David M.; Chan, Francis Ka‐Ming

doi:10.1016/j.tibs.2010.03.001

Cited by 138 publications

(125 citation statements)

References 69 publications

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“…RIP3-mediated necroptotic death requires RIP1 (27)(28)(29), a serine/threonine kinase that can also contribute to NF-κB signaling (30) and apoptosis. RIP1 −/− mice die shortly after birth (31), but fetal liver macrophages from RIP1 −/− mice, in contrast to RIP3 −/− macrophages, displayed a rescue from death induced by Y. pestis ( Fig.…”

Section: Significancementioning

confidence: 99%

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Weng

Marty-Roix

Ganesan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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266

263

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A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the "Black Death" in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF. Caspase-8 is known to mediate apoptotic death in response to infection with several viruses and to regulate programmed necrosis (necroptosis), but its role in bacterially induced cell death is poorly understood. Here we provide genetic evidence for a receptor-interacting protein (RIP) kinasecaspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF). Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing. Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents. Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge. Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death. We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.

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Section: Significancementioning

confidence: 99%

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Weng

Marty-Roix

Ganesan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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266

263

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“…While it has long been assumed that necrosis is predominantly a pathologic process resulting from tissue injury, there is growing evidence that cells can orchestrate their own demise through programmed cell necrosis in a manner that initiates physiologic inflammatory and repair responses. [2][3][4][6][7][8] Although anucleate, platelets have the capacity to undergo programmed cell death (Table 1). This has been most clearly demonstrated with platelet apoptosis; a process that is important for clearance of effete platelets from the circulation.…”

Section: Introductionmentioning

confidence: 99%

“…By initiating adaptive responses, necrosis may be considered as an important response to maintain tissue and organism integrity through the initiation of inflammatory and reparative responses. [2][3][4][6][7][8] Procoagulant platelets Phosphatidylserine (PS)-positive platelets capable of facilitating thrombin generation.Procoagulant apoptotic platelets Platelets induced to become procoagulant through a Bak/Bax-mediated apoptotic signaling pathway, in a manner dependent upon caspases but independent of platelet activation and granule release.Procoagulant necrotic platelets Platelets induced to become procoagulant through potent activation, leading to high sustained levels of cytosolic calcium, rapid mitochondrial dysfunction, and loss of membrane integrity. These platelets are also capable of initiating an inflammatory response.…”

mentioning

confidence: 99%

“…While traditionally viewed as an unregulated byproduct of severe pathologic injury, increasing evidence suggests that necrotic cells can elicit deliberate and controlled biologic responses that are important for host defense and repair. 3,4,7,8 Thus, necrotic cell death may have evolved as an early warning system to stimulate immune responses and repair mechanisms in organ systems that have sustained damage or invasion. This has become increasingly apparent in the context of viral and microbial infections, in which pathogen-induced necrotic death of cells of the host's immune system helps signal an inflammatory response.…”

mentioning

confidence: 99%

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Procoagulant platelets: are they necrotic?

Jackson

Schoenwaelder

2010

Blood

143

141

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Apoptosis and necrosis represent distinct cell death processes that regulate mammalian development, physiology and disease. Apoptosis characteristically leads to the silent destruction and removal of cells in the absence of an inflammatory response. In contrast, necrotic cell death can induce physiologic inflammatory responses linked to tissue defense and repair. Although anucleate, platelets undergo programmed cell death, with apoptosis playing an important role in clearing effete platelets from the circulation. While it has long been recognized that procoagulant platelets exhibit characteristic features of dying cells, recent studies have demonstrated that platelet procoagulant function can occur independent of apoptosis. A growing body of evidence suggest that the biochemical, morphologic and functional changes underlying agonist-induced platelet procoagulant function are broadly consistent with cell necrosis, raising the possibility that distinct death pathways regulate platelet function and survival. In this article, we will discuss the mechanisms underlying apoptotic and necrotic cell death pathways and examine the evidence linking these pathways to the platelet procoagulant response. We will also discuss the potential contribution of these pathways to the platelet storage lesion and propose a simplified nomenclature to describe procoagulant platelets. IntroductionUntil the early 1970s it was thought that all cells die as a result of necrosis (Table 1); a form of cell death that is prominent when tissues undergo extensive damage from trauma or disease. This concept changed dramatically in 1972 after the landmark observations of Kerr and colleagues, 9 who described a new form of cell death, termed apoptosis (Table 1). Since then, the genetic and biochemical processes responsible for apoptotic cell death have been extensively investigated. It is now well defined that apoptosis is a key process underlying human development, normal physiology and a range of common human diseases. 10 In contrast, the concepts underlying necrosis have become less clear-cut. While it has long been assumed that necrosis is predominantly a pathologic process resulting from tissue injury, there is growing evidence that cells can orchestrate their own demise through programmed cell necrosis in a manner that initiates physiologic inflammatory and repair responses. [2][3][4][6][7][8] Although anucleate, platelets have the capacity to undergo programmed cell death (Table 1). This has been most clearly demonstrated with platelet apoptosis; a process that is important for clearance of effete platelets from the circulation. 1,11 Many of the features of apoptosis (membrane fragmentation, cytoskeletal disruption, microvesiculation, caspase activation and phosphatidylserine [PS] exposure) are observed during prolonged platelet storage ex vivo and during the conversion of activated platelets to a procoagulant state, raising the possibility that apoptosis may also regulate platelet function. However, recent studies have demonstrated that the m...

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“…The serine threonine kinase RIP, a death domain-containing binding partner of Fas, was demonstrated as a crucial factor of cell death receptor-induced necrosis (35,36), and the Fas-induced apoptotic pathway was not affected in RIPdeficient cells (37,38) unless FasL was expressed on the membrane of Vsec (39,40). RIP has also been shown to be important for the FasL-independent activation of Fas-mediated apoptotic pathway through anoikis (41).…”

mentioning

confidence: 99%

Vesicles Released by Activated T Cells Induce Both Fas-Mediated RIP-Dependent Apoptotic and Fas-Independent Nonapoptotic Cell Deaths

Koncz

Hancz

Chakrabandhu

et al. 2012

The Journal of Immunology

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Activated T cells secrete Fas ligand (FasL)-containing vesicles (secreted vesicles) that induce death of target cells. We provide evidence that secreted vesicles from culture supernatants (Csup) of various origins are able to generate both Fas-dependent apoptotic and Fas-independent, nonapoptotic cell death. In the absence of Fas, the nonapoptotic, Fas-independent pathway could still induce cell death. In contrast to RIP-independent classical Fas-induced cell death triggered by cross-linked or membrane-bound FasL, CSup-derived stimuli-induced apoptosis exhibited unique molecular and enzymatic characteristics. It could be partially inhibited by blocking cathepsin D enzyme activity and required the presence of RIP. Whereas stimulation with CSup, derived from both FasL-overexpressing Jurkat cells and PBMC, could induce cell death, the requirements for Fas-associated death domain protein and caspase-9 were different between the two systems. Our study highlights an important distinction between cell contact-mediated and secreted vesicle-generated activation-induced cell death and also demonstrates that the type of the secreted vesicles can also modify the cell death route. We propose that besides cell-to-cell interaction-mediated Fas triggering, stimuli induced by secreted vesicles can mediate important additional cell death signals regulating activation-induced cell death under physiological conditions.

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The molecular regulation of programmed necrotic cell injury

Cited by 138 publications

References 69 publications

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Procoagulant platelets: are they necrotic?

Vesicles Released by Activated T Cells Induce Both Fas-Mediated RIP-Dependent Apoptotic and Fas-Independent Nonapoptotic Cell Deaths

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