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Granzyme B, Human, 1.3_960 U_ml, ELISA Kit, includes Mab coating Ab, control, standard, Biotin secondary, HRP_Streptavidin, buffer, substrate (No plate)

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[#CLBM1936] Granzyme B, Human, 1.3_960 U_ml, ELISA Kit, includes Mab coating Ab, control, standard, Biotin secondary, HRP_Streptavidin, buffer, substrate (No plate)


CLBM1936 | Granzyme B, Human, 1.3_960 U_ml, ELISA Kit, includes Mab coating Ab, control, standard, Biotin secondary, HRP_Streptavidin, buffer, substrate (No plate), kit
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(1) Triple-negative and HER2-overexpressing breast cancer cell sialylation impacts tumor microenvironment T-lymphocyte subset recruitment: a possible mechanism of tumor escape.[TOP]

Pubmed ID :29765252
Publication Date : //
Breast cancers develop different patterns of sialylation to modulate their tumor-infiltrating lymphocyte (TIL) environment. We studied the relationship between α-2,6 sialyltransferases and the TIL in different breast cancer molecular subgroups.

Authors : Garbar Christian, Mascaux Corinne, Merrouche Yacine, Bensussan Armand,

(2) Overarching Immunodominance Patterns and Substantial Diversity in Specificity and Functionality in the Circulating Human Influenza A and B CD4 T Cell Repertoire.[TOP]

Pubmed ID :29762692
Publication Date : //
There is limited information on the antigen specificity and functional potential of the influenza-specific CD4 T cell repertoire in humans. Here, ELISPOT assays were used to examine circulating CD4 T cell influenza specificities directly ex vivo in healthy adults.  Our studies revealed CD4 T cell reactivity to multiple influenza proteins, including hemagglutinins, NA, M1 and NP. Unexpectedly, the immunodominance hierarchies and functional potential of cells reactive toward influenza A were distinct from influenza B. We also identified influenza-specific cells producing granzyme B. Our findings revealed individual and virus-specific patterns that may differentially poise humans to respond to infection or vaccination.

Authors : Richards Katherine A, Treanor John J, Nayak Jennifer L, Sant Andrea J,

(3) Proteomic definition of human mucosal-associated invariant T cells determines their unique molecular effector phenotype.[TOP]

Pubmed ID :29749611
Publication Date : //
Mucosal-associated invariant T cells (MAIT) constitute the most abundant anti-bacterial CD8 T cell population in humans. MR1/TCR-activated MAIT cells were reported to organize cytotoxic and innate-like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3+Vα7.2+CD161+) in comparison with those from conventional non-MAIT CD8 T cells (cCD8 ) and NK cells. Quantitative mass spectrometry characterized 5500 proteins of primary MAIT cells and identified 160 and 135 proteins that discriminate them from cCD8 T cells and NK cells donor-independently. Most notably, MAIT cells showed a unique exocytosis machinery in parallel to a pro-inflammatory granzyme profile with high levels of the granzymes A, K and M. Furthermore, 24 proteins were identified with highest abundances in MAIT cells, including CD26, CD98 and L-amino-oxidase (LAAO). Among those, expression of granzyme K and CD98 were validated as MAIT-specific with respect to non-MAIT CD8 effector subsets and LAAO was found to be recruited together with granzymes, perforin and CD107a at the immunological synapse of activated MAIT cells. In conclusion, this study complements knowledge on the molecular effector phenotype of MAIT cells and suggest novel immune regulatory functions as part of their cytotoxic responses. This article is protected by copyright. All rights reserved.

Authors : Bulitta Björn, Zuschratter Werner, Bernal Isabel, Bruder Dunja, Klawonn Frank, von Bergen Martin, Garritsen Henrikus Stephanus Paulus, Jänsch Lothar,

(4) Antigenicity of -Activated C-Kinase Antigen (LACK) in Human Peripheral Blood Mononuclear Cells, and Protective Effect of Prime-Boost Vaccination With pCI-neo-LACK Plus Attenuated LACK-Expressing Vaccinia Viruses in Hamsters.[TOP]

Pubmed ID :29740446
Publication Date : //
-activated C-kinase antigen (LACK) is a highly conserved protein among species and is considered a viable vaccine candidate for human leishmaniasis. In animal models, prime-boost vaccination with LACK-expressing plasmids plus attenuated vaccinia viruses (modified vaccinia Ankara [MVA] and mutant M65) expressing LACK, has been shown to protect against cutaneous leishmaniasis (CL). Further, LACK demonstrated to induce the production of protective cytokines in patients with active CL or cured visceral leishmaniasis, as well as in asymptomatic individuals from endemic areas. However, whether LACK is capable to trigger cytokine release by peripheral blood mononuclear cells from patients cured of CL due to () or induce protection in -infected hamsters [visceral leishmaniasis (VL) model], has not yet been analyzed. The present work examines the immunogenicity of LACK in cured VL and CL patients, and asymptomatic subjects from an area. It also evaluates the vaccine potential of LACK against infection in hamsters, in a protocol of priming with plasmid pCI-neo-LACK (DNA-LACK) followed by a booster with the poxvirus vectors MVA-LACK or M65-LACK. LACK-stimulated PBMC from both asymptomatic and cured subjects responded by producing IFN-γ, TNF-α, and granzyme B (Th1-type response). Further, 78% of PBMC samples that responded to soluble antigen showed IFN-γ secretion following stimulation with LACK. In hamsters, the protocol of DNA-LACK prime/MVA-LACK or M65-LACK virus boost vaccination significantly reduced the amount of DNA in the liver and bone marrow, with no differences recorded between the use of MVA or M65 virus vector options. In summary, the Th1-type and cytotoxic responses elicited by LACK in PBMC from human subjects infected with , and the parasite protective effect of prime/boost vaccination in hamsters with DNA-LACK/MVA-LACK and DNA-LACK/M65-LACK, revealed the significance of LACK in activating human and hamster immune responses and support LACK to be a valuable candidate for inclusion in a vaccine against human VL.

Authors : Fernández Laura, Carrillo Eugenia, Sánchez-Sampedro Lucas, Sánchez Carmen, Ibarra-Meneses Ana Victoria, Jimenez M Angeles, Almeida Valter Dos Anjos, Esteban Mariano, Moreno Javier,

(5) Unique and Common Features of Innate-Like Human Vδ2 γδT Cells and Mucosal-Associated Invariant T Cells.[TOP]

Pubmed ID :29740432
Publication Date : //
Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans that can be activated in a TCR-independent manner by inflammatory and antiviral cytokines. In humans, the capacity for TCR-independent activation is functionally linked to a transcriptional program that can be identified by the expression of the C-type lectin receptor, CD161. In addition to MAIT cells, it has been demonstrated that a subset of γδT cells expresses CD161 and can be activated by TCR-independent cytokine stimulation. In this study, we sought to clarify the nature of cytokine-responsive human γδT cells. We could link CD161 expression on Vδ2 versus Vδ1 γδT cells to the observation that Vδ2 γδT cells, but not Vδ1 γδT cells, robustly produced IFN-γ upon stimulation with a variety of cytokine combinations. Interestingly, both CD161 and CD161 Vδ2 γδT cells responded to these stimuli, with increased functionality within the CD161 subset. This innate-like responsiveness corresponded to high expression of PLZF and IL-18Rα, analogous to MAIT cells. Vδ2 γδT cells in human duodenum and liver maintained a CD161 IL-18Rα phenotype and produced IFN-γ in response to IL-12 and IL-18 stimulation. In contrast to MAIT cells, we could not detect IL-17A production but observed higher steady-state expression of Granzyme B by Vδ2 γδT cells. Finally, we investigated the frequency and functionality of γδT cells in the context of chronic hepatitis C virus infection, as MAIT cells are reduced in frequency in this disease. By contrast, Vδ2 γδT cells were maintained in frequency and displayed unimpaired IFN-γ production in response to cytokine stimulation. In sum, human Vδ2 γδT cells are a functionally distinct population of cytokine-responsive innate-like T cells that is abundant in blood and tissues with similarities to human MAIT cells.

Authors : Provine Nicholas M, Binder Benedikt, FitzPatrick Michael E B, Schuch Anita, Garner Lucy C, Williamson Kate D, van Wilgenburg Bonnie, Thimme Robert, Klenerman Paul, Hofmann Maike,

(6) hIL-15-gene modified human natural killer cells (NKL-IL15) exhibit anti-human leukemia functions.[TOP]

Pubmed ID :29737430
Publication Date : //
Natural killer (NK) cells can kill transformed cells and represent anti-tumor activities for improving the immunotherapy of cancer. In previous works, we established human interleukin-15 (hIL-15) gene-modified NKL cells (NKL-IL15) and demonstrated their efficiency against human hepatocarcinoma cells (HCCs) in vitro and in vivo. To further assess the applicability of NKL-IL15 cells in adoptive cellular immunotherapy for human leukemia, here we report their natural cytotoxicity against leukemia in vitro and in vivo.

Authors : Jiang Wen, Zhang Cai, Tian Zhigang, Zhang Jian,

(7) Rift valley fever viral load correlates with the human inflammatory response and coagulation pathway abnormalities in humans with hemorrhagic manifestations.[TOP]

Pubmed ID :29727450
Publication Date : //
Rift Valley fever virus is an arbovirus that affects both livestock and humans throughout Africa and in the Middle East. Despite its endemicity throughout Africa, it is a rare event to identify an infected individual during the acute phase of the disease and an even rarer event to collect serial blood samples from the affected patient. Severely affected patients can present with hemorrhagic manifestations of disease. In this study we identified three Ugandan men with RVFV disease that was accompanied by hemorrhagic manifestations. Serial blood samples from these men were analyzed for a series of biomarkers specific for various aspects of human pathophysiology including inflammation, endothelial function and coagulopathy. There were significant differences between biomarker levels in controls and cases both early during the illness and after clearance of viremia. Positive correlation of viral load with markers of inflammation (IP-10, CRP, Eotaxin, MCP-2 and Granzyme B), markers of fibrinolysis (tPA and D-dimer), and markers of endothelial function (sICAM-1) were all noted. However, and perhaps most interesting given the fact that these individuals exhibited hemorrhagic manifestations of disease, was the finding of a negative correlation between viral load and P-selectin, ADAMTS13, and fibrinogen all of which are associated with coagulation pathways occurring on the endothelial surface.

Authors : de St Maurice Annabelle, Harmon Jessica, Nyakarahuka Luke, Balinandi Stephen, Tumusiime Alex, Kyondo Jackson, Mulei Sophia, Namutebi Annemarion, Knust Barbara, Shoemaker Trevor, Nichol Stuart T, McElroy Anita K, Spiropoulou Christina F,

(8) Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding.[TOP]

Pubmed ID :29703634
Publication Date : //
Subendothelial interaction of LDL with extracellular matrix drives atherogenesis. This interaction can be strengthened by proteolytic modification of LDL. Mast cells (MCs) are present in atherosclerotic lesions, and upon activation, they degranulate and release a variety of neutral proteases. Here we studied the ability of MC proteases to cleave apoB-100 of LDL and affect the binding of LDL to proteoglycans.

Authors : Maaninka Katariina, Nguyen Su Duy, Mäyränpää Mikko I, Plihtari Riia, Rajamäki Kristiina, Lindsberg Perttu J, Kovanen Petri T, Öörni Katariina,

(9) The early expansion of anergic NKG2Apos/CD56dim/CD16neg natural killer cells represents a therapeutic target in haploidentical haematopoietic stem cell transplantation.[TOP]

Pubmed ID :29700172
Publication Date : //
Natural Killer cells are the first lymphocyte population to reconstitute early after non myelo-ablative and T cell-replete haploidentical hematopoietic stem cell transplantation with post-transplant infusion of cyclophosphamide. The present study characterizes the transient and predominant expansion starting from the 2nd week after haploidentical hematopoietic stem cell transplantation of a donor-derived unconventional subset of NKp46neg-low/CD56dim/CD16neg natural killer cells expressing remarkable high levels of CD94/NKG2A. Both transcription and phenotypic profiles indicated that unconventional NKp46neg-low/CD56dim/CD16neg natural killer cells are a distinct natural killer cell subpopulation with features of late stage differentiation, yet retaining proliferative capability and functional plasticity to generate conventional NKp46pos/CD56bright/CD16pos natural killer cells in response to interleukin-15 plus interleukin-18. While present at low frequency in healthy donors, unconventional NKp46neg-low/CD56dim/CD16neg natural killer cells are greatly expanded in the following 7 weeks after haploidentical hematopoietic stem cell transplantation and express high levels of the activating receptors NKGD and NKp30 as well as of the lytic granules Granzyme-B and Perforin. Nonetheless, NKp46neg-low/CD56dim/CD16neg natural killer cells displayed a markedly defective cytotoxicity that could be reversed by blocking the inhibitory receptor CD94/NKG2A. These data open new important perspectives to better understand the ontogenesis/homeostasis of human natural killer cells and to develop a novel immune-therapeutic approach that targets the inhibitory NKG2A check point, thus unleashing natural killer cell alloreactivity early after haploidentical hematopoietic stem cell transplantation.

Authors : Roberto Alessandra, Di Vito Clara, Zaghi Elisa, Mazza Emilia Maria Cristina, Capucetti Arianna, Calvi Michela, Tentorio Paolo, Zanon Veronica, Sarina Barbara, Mariotti Jacopo, Bramanti Stefania, Tenedini Elena, Tagliafico Enrico, Bicciato Silvio, Santoro Armando, Roederer Mario, Marcenaro Emanuela, Castagna Luca, Lugli Enrico, Mavilio Domenico,

(10) IL-21 Increases the Reactivity of Allogeneic Human Vγ9Vδ2 T Cells Against Primary Glioblastoma Tumors.[TOP]

Pubmed ID :29683891
Publication Date : //
Glioblastoma multiforme (GBM) remains the most frequent and deadliest primary brain tumor in adults despite aggressive treatments, because of the persistence of infiltrative and resistant tumor cells. Nonalloreactive human Vγ9Vδ2 T lymphocytes, the major peripheral γδ T-cell subset in adults, represent attractive effectors for designing immunotherapeutic strategies to track and eliminate brain tumor cells, with limited side effects. We analyzed the effects of ex vivo sensitizations of Vγ9Vδ2 T cells by IL-21, a modulating cytokine, on their cytolytic reactivity. We first showed that primary human GBM-1 cells were naturally eliminated by allogeneic Vγ9Vδ2 T lymphocytes, through a perforin/granzyme-mediated cytotoxicity. IL-21 increased both intracellular granzyme B levels and cytotoxicity of allogeneic human Vγ9Vδ2 T lymphocytes in vitro. Importantly, IL-21-enhanced cytotoxicity was rapid, which supports the development of sensitization(s) of γδ T lymphocytes before adoptive transfer, a process that avoids any deleterious effect associated with direct administrations of IL-21. Finally, we showed, for the first time, that IL-21-sensitized allogeneic Vγ9Vδ2 T cells significantly eliminated GBM tumor cells that developed in the brain after orthotopic administrations in vivo. Altogether our observations pave the way for novel efficient stereotaxic immunotherapies in GBM patients by using IL-21-sensitized allogeneic human Vγ9Vδ2 T cells.

Authors : Joalland Noémie, Chauvin Cynthia, Oliver Lisa, Vallette François M, Pecqueur Claire, Jarry Ulrich, Scotet Emmanuel,