Granzymes in disease: bench to bedside

Granville, David J.

doi:10.1038/cdd.2009.218

Cited by 38 publications

(31 citation statements)

References 17 publications

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“…Cytotoxic T lymphocytes and natural killer cells secrete granzyme and perforin to initiate granule-mediated apoptosis. Granzyme enters the target cell with the help of perforin to activate caspases [37,38]. Granzyme and perforin have been sequenced in different fishes, including the olive flounder; revealing closer homology with their mammalian counterparts [39e45].…”

Section: Discussionmentioning

confidence: 99%

Temperature-dependent viral replication and antiviral apoptotic response in viral haemorrhagic septicaemia virus (VHSV)-infected olive flounder (Paralichthys olivaceus)

Avunje

Kim

et al. 2012

Fish & Shellfish Immunology

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Section: Discussionmentioning

confidence: 99%

Temperature-dependent viral replication and antiviral apoptotic response in viral haemorrhagic septicaemia virus (VHSV)-infected olive flounder (Paralichthys olivaceus)

Avunje

Kim

et al. 2012

Fish & Shellfish Immunology

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“…However, gzmK is also up-regulated in different inflammatory diseases, among them artherosclerosis, arthritis, chronic pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma and sepsis (Boivin et al, 2009;Granville, 2010;Heutinck et al, 2010). In the case of sepsis, elevated levels of free, active gzmK and decreased levels of an endogenous inhibitor inter-alpha inhibitor protein (IAIP) correlate with the severity of the pathology (Lim et al, 2003;Rucevic et al, 2007;Singh et al, 2010).…”

Section: Granzyme Kmentioning

confidence: 98%

Are all granzymes cytotoxicin vivo?

Joeckel

Bird

2014

Biological Chemistry

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Granzymes are serine proteases mainly found in cytotoxic lymphocytes. The most-studied member of this group is granzyme B, which is a potent cytotoxin that has set the paradigm that all granzymes are cyototoxic. In the last 5 years, this paradigm has become controversial. On one hand, there is a plethora of sometimes contradictory publications showing mainly caspase-independent cytotoxic effects of granzyme A and the so-called orphan granzymes in vitro. On the other hand, there are increasing numbers of reports of granzymes failing to induce cell death in vitro unless very high (potentially supra-physiological) concentrations are used. Furthermore, experiments with granzyme A or granzyme M knock-out mice reveal little or no deficit in their cytotoxic lymphocytes' killing ability ex vivo, but indicate impairment in the inflammatory response. These findings of non-cytotoxic effects of granzymes challenge dogma, and thus require alternative or additional explanations to be developed of the role of granzymes in defeating pathogens. Here we review evidence for granzyme cytotoxicity, give an overview of their non-cytotoxic functions, and suggest technical improvements for future investigations.

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“…The accumulation of GrB in putatively terminally differentiated CD8 + T-cells in the absence of perforin in vivo (147) suggests that GrB may be released into and accumulate in the extracellular space, resulting in inflammation and tissue damage (148–150). It has also been shown that ex vivo live influenza virus challenge results in a lower GrB response in CMV-seropositive compared to -seronegative older adults (63), further suggesting an impairment of CTL response to influenza mediated by CMV.…”

Section: The Role Of T-cells In Influenza Infection and Vaccinationmentioning

confidence: 99%

Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection

et al. 2017

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The number of people over the age of 60 is expected to double by 2050 according to the WHO. This emphasizes the need to ensure optimized resilience to health stressors in late life. In older adults, influenza is one of the leading causes of catastrophic disability (defined as the loss of independence in daily living and self-care activities). Influenza vaccination is generally perceived to be less protective in older adults, with some studies suggesting that the humoral immune response to the vaccine is further impaired in cytomegalovirus (CMV)-seropositive older people. CMV is a β-herpes virus infection that is generally asymptomatic in healthy individuals. The majority of older adults possess serum antibodies against the virus indicating latent infection. Age-related changes in T-cell-mediated immunity are augmented by CMV infection and may be associated with more serious complications of influenza infection. This review focuses on the impact of aging and CMV on immune cell function, the response to influenza infection and vaccination, and how the current understanding of aging and CMV can be used to design a more effective influenza vaccine for older adults. It is anticipated that efforts in this field will address the public health need for improved protection against influenza in older adults, particularly with regard to the serious complications leading to loss of independence.

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Granzymes in disease: bench to bedside

Cited by 38 publications

References 17 publications

Temperature-dependent viral replication and antiviral apoptotic response in viral haemorrhagic septicaemia virus (VHSV)-infected olive flounder (Paralichthys olivaceus)

Temperature-dependent viral replication and antiviral apoptotic response in viral haemorrhagic septicaemia virus (VHSV)-infected olive flounder (Paralichthys olivaceus)

Are all granzymes cytotoxicin vivo?

Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection

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