Granzyme B Expression Is Enhanced in Human Monocytes by TLR8 Agonists and Contributes to Antibody-Dependent Cellular Cytotoxicity

Elavazhagan, Saranya; Fatehchand, Kavin; Santhanam, Vikram; Fang, Huiqing; Li, Ren; Gautam, Shalini; Reader, Brenda F.; Mo, Xiaokui; Cheney, Carolyn; Briercheck, Edward L.; Vasilakos, John P.; Dietsch, Gregory N.; Hershberg, Robert M.; Caligiuri, Michael A.; Byrd, John C.; Butchar, Jonathan P.; Tridandapani, Susheela

doi:10.4049/jimmunol.1402316

Cited by 40 publications

(29 citation statements)

References 59 publications

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“…GZMB is expressed in cytotoxic T lymphocytes (CTL) and NK cells and is primary mediator of apoptosis by CTL in cell-mediated immune response. GZMB seems to play critical role antibody –dependent cellular cytotoxicity ( Elavazhagan et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA–mRNA Pairs Associated with Outcome in AML: From In Vitro Cell-Based Studies to AML Patients

et al. 2016

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Cytarabine is the primary chemotherapeutic agent used for treatment of acute myeloid leukemia (AML). Disease relapse after initial remission remains one of the most pressing therapeutic challenges in the treatment of AML. Relapsed disease is often resistant to cytarabine and subsequent salvage therapy is ineffective. Recent studies have shown that some microRNAs (miRNAs) are associated with prognosis, but have not yet explored the role of miRNAs in cellular response to cytarabine. We identified 20 miRNAs that associate with the in vitro cytarabine chemo-sensitivity or apoptotic response of eight AML cell lines. Out of the 20 miRNAs, data on 18 miRNAs was available in AML patients from The Cancer Genome Atlas database. Our stepwise-integrated analyses (step 1 – miRNA–target mRNA that were significantly correlated in AML patients; step 2 – mRNAs from step 1 with significant association with overall survival (OS)) identified 23 unique miRNA–mRNA pairs predictive of OS in AML patients. As expected HOX genes (HOXA9, HOXB7, and HOXA10) were identified to be regulated by miRs as well as predictive of worse OS. Additionally, miR107-Myb, miR-378-granzyme B involved in granzyme signaling and miR10a-MAP4K4 were identified to be predictive of outcome through integrated analysis. Although additional functional validations to establish clinical/pharmacologic importance of miRNA–mRNA pairs are needed, our results from RNA electrophoretic mobility shift assay confirmed binding of miR-10a, miR-378, and miR-107 with their target genes GALNT1, GZMB, and MYB, respectively. Integration of pathogenic and pharmacologically significant miRNAs and miRNA–mRNA relationships identified in our study opens up opportunities for development of targeted/miRNA-directed therapies.

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Section: Discussionmentioning

confidence: 99%

MicroRNA–mRNA Pairs Associated with Outcome in AML: From In Vitro Cell-Based Studies to AML Patients

et al. 2016

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“…FcγRIV is also expressed on murine monocytes/macrophages and neutrophils, but not on NK cells . While some mechanistic conservation between NK cell‐ and monocyte‐mediated ADCC has been demonstrated, the mechanism underlying neutrophil‐mediated ADCC is only currently being investigated. Disparities between human and mouse FcRs represent a limitation of murine studies, but FcγR‐humanized mice have been developed to partially overcome this limitation …”

Section: Fc‐mediated Effector Functions Of Antibodies and Fcrsmentioning

confidence: 99%

The protective potential of Fc‐mediated antibody functions against influenza virus and other viral pathogens

Vanderven

Kent

2020

Immunol Cell Biol

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In recent years, there has been a renewed interest in utilizing antibody fragment crystallizable (Fc) functions to prevent and control viral infections. The protective and therapeutic potential of Fc‐mediated antibody functions have been assessed for some clinically important human viruses, including HIV, hemorrhagic fever viruses and influenza virus. There is mounting evidence that influenza‐specific antibodies with Fc‐mediated functions, such as antibody‐dependent cellular cytotoxicity and antibody‐dependent phagocytosis, can aid in the clearance of influenza virus infection. Recent influenza challenge studies and intravenous immunoglobulin G therapy studies in humans suggest a protective role for Fc effector functions in vivo. Broadly reactive influenza antibodies with Fc‐mediated functions are prevalent in the human population and could inform the development of a universally protective influenza vaccine or therapy. In this review, we explore the utility of antibodies with Fc‐mediated effector functions against viral infections with a focus on influenza virus.

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“…Известно, что в иммунной системе человека имеется большое количество компенсаторных механизмов, позволяющих сохранять длительное время ее функционирование на нормальном уровне. Моноциты, как и НК клетки, могут осуществлять цитотоксический эффект с помощью контактного взаимодействия с мишенями [17]. Кроме того, многие авторы рассматривают их как клетки, регулирующие уровень функционирования естественной цито-иммунология шизофрении токсичности НК лимфоцитов у здоровых и больных при разных формах патологии [18,19].…”

Section: материал и методыunclassified

The cellular factors of innate immunity in nonpsychotic patients at high risk for schizophrenia

Vasilyeva¹,

Sg²,

Factor³

et al. 2016

Z. nevrol. psikhiatr. im. S.S. Korsakova

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Compared to controls, patients had the lower PhI level (p<0.001) which was compensated by the increase in PhN levels, and the lower NK CA level which was increased due to the influence of monocytes. Negative correlations between PhI and PhN (r= -0.83, p<0.01) and between the level of NKCA and PhI (r= -0.83, p<0.05) as well as the positive correlation between PhN and SOPS scores (r=0.69, p<0.01) were found. After treatment, there was the decreasein the severity of mental disorders (p<0.001). The level of PhAN was normalized in 61.9% of patients compared to 36.7% before treatment. After treatment, the proportion of patients with normal levels of NK CA was the same as before treatment (40 and 35%, respectively). The immune disturbances revealed in the study may play a role in the pathogenesis of the disease and have predictive value for schizophrenia.

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Granzyme B Expression Is Enhanced in Human Monocytes by TLR8 Agonists and Contributes to Antibody-Dependent Cellular Cytotoxicity

Cited by 40 publications

References 59 publications

MicroRNA–mRNA Pairs Associated with Outcome in AML: From In Vitro Cell-Based Studies to AML Patients

MicroRNA–mRNA Pairs Associated with Outcome in AML: From In Vitro Cell-Based Studies to AML Patients

The protective potential of Fc‐mediated antibody functions against influenza virus and other viral pathogens

The cellular factors of innate immunity in nonpsychotic patients at high risk for schizophrenia

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