Human cytotoxic lymphocyte granzyme B. Its purification from granules and the characterization of substrate and inhibitor specificity.

Poe, Martin; Blake, J T; Boulton, D. A.; Gammon, Maureen C.; Sigal, Nolan H.; Wu, Joseph K.; Zweerink, Hans J.

doi:10.1016/s0021-9258(18)52407-8

Cited by 166 publications

(25 citation statements)

References 68 publications

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“…This buffer system mimicked the pH condition in lytic granules and has been used for DPPI to process and activate pro-gzmB. We confirmed that gzmB could maintain ∼25% of its activity under the acidic condition, consistent with an early study ( 71 ). Taking into account that granule-released, serglycin-bound gzmB could trigger apoptosis of target cells as efficient as free enzymes ( 72 ), we believe the activation and retention of G-SNAT-Cy5 within CTLs are dependent on the gzmB activity.…”

Section: Discussionsupporting

confidence: 89%

Multi-parameter optical imaging of immune cell activity in chimeric antigen receptor T-cell and checkpoint blockade therapies

Xie

Rami

Zhou

et al. 2021

Preprint

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Longitudinal multimodal imaging presents unique opportunities for noninvasive surveillance and prediction of treatment response to cancer immunotherapy. In this work we first designed a novel granzyme B activated self-assembly small molecule, G-SNAT, for quantitative assessment of cytotoxic T lymphocyte mediated cancer cell killing in vivo. In lymphoma tumor bearing mice, the retention of cyanine 5 labeled G-SNAT-Cy5 was shown to be highly correlated to CAR T-cell mediated granzyme B release and tumor eradication. In colorectal tumor-bearing transgenic mice, expressing firefly luciferase in hematopoietic cells, and which received combination treatment of anti-PD-1 and anti-CTLA-4, longitudinal bioluminescence and fluorescence imaging revealed the dynamics of immune cell expansion, trafficking, tumor infiltration, and cytotoxic activity which predicted therapeutic outcome before tumor shrinkage was evident. These results support further development of G-SNAT for imaging early immune response to checkpoint blockade and CAR T-cell therapy in patients and highlight the utility of multimodality imaging for improved mechanistic insights into cancer immunotherapy.

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Section: Discussionsupporting

confidence: 89%

Multi-parameter optical imaging of immune cell activity in chimeric antigen receptor T-cell and checkpoint blockade therapies

Xie

Rami

Zhou

et al. 2021

Preprint

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“…Granzymes are serine proteinases that are contained in cytotoxic lymphocyte granules (natural killer cells and cytotoxic T lymphocytes). They are considered to be instrumental in cytotoxicity via apoptosis (Hayes et al, 1989;Poe et al, 1991;Shi et al, 1992;Heusel et al, 1994). Recently, McElwee Apoptosis is seen in the normal epidermis and in the matrix of cycling hair (Weedon and Strutton, 1981).…”

Section: Discussionmentioning

confidence: 99%

Role of Cytotoxic T Cells in Chronic Alopecia Areata

Bodemer¹,

Peuchmaur²,

Fraitaig

et al. 2000

Journal of Investigative Dermatology

118

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Cytokines play a role in alopecia areata. We used immunohistochemical and in situ hybridization studies to demonstrate the persistence of pro-inflammatory as well as apoptotic mechanisms in skin biopsies from patients with chronic alopecia areata. In situ hybridization allows the visualization of the distribution of immunocompetent cells in vivo. We studied skin biopsies from 11 untreated alopecia areata patients and two normal controls. In situ hybridization was performed on frozen sections using 35S-radio-labeled riboprobes, specific for IL-1beta, IL-2, IL-6, INFgamma, and granzyme B mRNA. Immunohistochemistry was carried out using an anti-IL-1beta monoclonal antibody, and a monoclonal antibody directed against the human Fas protein. We demonstrated the presence of cells labeled with IL-1beta, IL-6, INFgamma, and granzyme B antisense probes. Similarly, cells labeled with anti-IL-1beta were found in 10 of 11 cases. The labeled cells were located in the mononuclear peri- and intrafollicular infiltrate. Cells expressing granzyme B were found in close contact with the follicle. Fas positivity was demonstrated in four of four cases at the level of the cytoplasmic membrane of the hair follicle keratinocytes. These results, based on visualizing the labeled cells, demonstrate that pro-inflammatory cytokines are produced by the mononuclear cell infiltrate in close contact with follicles in alopecia areata. Furthermore, they demonstrate for the first time that apoptotic mechanisms involving granzyme B and Fas-Fas ligand pathways may play a major role in the persistence of chronic alopecia areata.

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“…For example, MMPs are inhibited by binding of their internal inhibitors: tissue inhibitors of MMPs (TIMPs) in a 1 to 1 molar stoichiometric fashion. It has been reported that granzyme B is efficiently inhibited by ␣1-antitrypsin and to a lesser extent by ␣2macrogloblin [47]. However, other reports showed that the inhibitory action of ␣1-antitrypsin for granzyme B is still controversial [48,49].…”

Section: Inhibition Of Granzyme Bmentioning

confidence: 99%

Granzyme B as a novel factor involved in cardiovascular diseases

Saito¹,

Kondo

Hojo

2011

Journal of Cardiology

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Apoptosis plays an important role in cardiovascular diseases such as atherosclerosis, ischemic heart disease, and congestive heart failure. Previous studies have demonstrated that oxidative stress, physiological stress, and inflammatory cytokines such as tumor necrosis factor and Fas ligand are involved in apoptosis of cardiovascular system. We demonstrate that another apoptosis-related pathway, i.e. granzyme B/perforin system is involved in cardiovascular diseases. Expression of granzyme B, a member of serine protease family is increased in acute coronary syndrome, coronary artery disease with end-stage renal disease, and subacute stage of acute myocardial infarction. Although granzyme B is extensively researched in immunological disorders, the role of granzyme B/perforin system was not clear in the cardiovascular field. In addition, little is known regarding the inhibition of granzyme B system in the clinical situation. In this review we demonstrate recent findings of granzyme B in cardiovascular diseases and possible therapeutic applications of inhibiting the granzyme B/perforin system.

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Human cytotoxic lymphocyte granzyme B. Its purification from granules and the characterization of substrate and inhibitor specificity.

Cited by 166 publications

References 68 publications

Multi-parameter optical imaging of immune cell activity in chimeric antigen receptor T-cell and checkpoint blockade therapies

Multi-parameter optical imaging of immune cell activity in chimeric antigen receptor T-cell and checkpoint blockade therapies

Role of Cytotoxic T Cells in Chronic Alopecia Areata

Granzyme B as a novel factor involved in cardiovascular diseases

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