APOPTOSIS INDUCED BY γ IRRADIATION IN PERIPHERAL BLOOD MONONUCLEAR CELLS IS NOT MEDIATED BY CYTOCHROME-C RELEASE AND ONLY PARTIALLY INVOLVES CASPASE-3-LIKE PROTEASES

1999 ◽  
Vol 23 (9) ◽  
pp. 611-617 ◽  
Author(s):  
H Louagie
Keyword(s):  
Cytochrome C ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Cytochrome C Release ◽  
Γ Irradiation ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

scholarly journals Tissue-regenerative potential of the secretome of γ-irradiated peripheral blood mononuclear cells is mediated via TNFRSF1B-induced necroptosis

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Elisabeth Simader ◽  
Lucian Beer ◽  
Maria Laggner ◽  
Vera Vorstandlechner ◽  
Alfred Gugerell ◽  
...  
Keyword(s):  
Cell Death ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Bioactive Molecules ◽  
Γ Irradiation ◽  
Peripheral Blood Mononuclear ◽  
Angiogenic Activity ◽  
Angiogenic Potential ◽  
Blood Mononuclear Cells

Abstract Peripheral blood mononuclear cells (PBMCs) have been shown to produce and release a plethora of pro-angiogenetic factors in response to γ-irradiation, partially accounting for their tissue-regenerative capacity. Here, we investigated whether a certain cell subtype of PBMCs is responsible for this effect, and whether the type of cell death affects the pro-angiogenic potential of bioactive molecules released by γ-irradiated PBMCs. PBMCs and PBMC subpopulations, including CD4+ and CD8+ T cells, B cells, monocytes, and natural killer cells, were isolated and subjected to high-dose γ-irradiation. Transcriptome analysis revealed subpopulation-specific responses to γ-irradiation with distinct activation of pro-angiogenic pathways, cytokine production, and death receptor signalling. Analysis of the proteins released showed that interactions of the subsets are important for the generation of a pro-angiogenic secretome. This result was confirmed at the functional level by the finding that the secretome of γ-irradiated PBMCs displayed higher pro-angiogenic activity in an aortic ring assay. Scanning electron microscopy and image stream analysis of γ-irradiated PBMCs revealed distinct morphological changes, indicative for apoptotic and necroptotic cell death. While inhibition of apoptosis had no effect on the pro-angiogenic activity of the secretome, inhibiting necroptosis in stressed PBMCs abolished blood vessel sprouting. Mechanistically, we identified tumor necrosis factor (TNF) receptor superfamily member 1B as the main driver of necroptosis in response to γ-irradiation in PBMCs, which was most likely mediated via membrane-bound TNF-α. In conclusion, our study demonstrates that the pro-angiogenic activity of the secretome of γ-irradiated PBMCs requires interplay of different PBMC subpopulations. Furthermore, we show that TNF-dependent necroptosis is an indispensable molecular process for conferring tissue-regenerative activity and for the pro-angiogenic potential of the PBMC secretome. These findings contribute to a better understanding of secretome-based therapies in regenerative medicine.

scholarly journals Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Chien-Ming Chu ◽  
Li-Chung Chiu ◽  
Chung-Chieh Yu ◽  
Li-Pang Chuang ◽  
Kuo-Chin Kao ◽  
...  
Keyword(s):  
Cell Death ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
B Cell Lymphoma ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Background. Apoptosis is one of the causes of immune depression in sepsis. Pyroptosis also occurs in sepsis. The toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) have been shown to play important roles in apoptosis and pyroptosis. However, it is still unknown whether TLR4 inhibition decreases apoptosis in sepsis. Methods. Stimulated peripheral blood mononuclear cells (PBMCs) with or without lipopolysaccharides (LPS) and high-mobility group box 1 (HMGB1) were cultured with or without TLR4 inhibition using monoclonal antibodies from 20 patients with sepsis. Caspase-3, caspase-8, and caspase-9 activities were measured. The expression of B cell lymphoma 2 (Bcl2) and Bcl2-associated X (Bax) was measured. The cell death of PBMCs was detected using a flow cytofluorimeter. Results. After TLR4 inhibition, Bcl2 to Bax ratio elevated both in LPS and HMGB1-stimulated PBMCs. The activities of caspase-3, caspase-8, and caspase-9 did not change in LPS or HMGB1-stimulated PBMCs. The cell death of LPS and HMGB1-stimulated CD8 lymphocytes and monocytes increased after TLR4 inhibition. The cell death of CD4 lymphocytes was unchanged. Conclusion. The apoptosis did not decrease, while TLR4 was inhibited. After TLR4 inhibition, there was an unknown mechanism to keep cell death in stimulated PBMCs in patients with sepsis.

scholarly journals CASPASE-3 AKTIF DI LEUKEMIA MIELOSITIK AKUT (LMA) DAN LEUKEMIA LIMFOBLASTIK AKUT (LLA)

2016 ◽  
Vol 19 (3) ◽  
pp. 141
Author(s):  
Agus Setiawan ◽  
Indarini Indarini ◽  
Lyana Setiawan ◽  
Siti Boedina Kresno ◽  
Nugroho Prayogo ◽  
...  
Keyword(s):  
Complete Remission ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Clinical Pathology ◽  
Induction Treatment ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Active Caspase

Dysregulation of apoptosis plays an essential role either in leukemogenesis or treatment response. Caspase-3 is a cysteine protease that functions as the final common mediator of apoptosis. The expression of the active caspase-3 is presumed as a predictor of prognosis and is able to predict the chemotherapy sensitivity. The aim of this study is to identify and to know the profile of active caspase-3 in Acute Myeloid Leukaemia (AML) and Acute Lymphoblastic Leukaemia (ALL), to correlate its expression in marrow and peripheral blood mononuclear cells, and to verify the extent of its use as a complete remission predictor after induction treatment. The study subjects consisted of patients who were diagnosed as AML and ALL with marrow and peripheral blood examination performed at the Department of Clinical Pathology Dharmais Cancer Hospital and CiptoMangunkusumo Hospital. Based on this study, it is revealed that the active caspase-3 expression in mononuclear marrow cells was higher in AML compared to ALL (p=0.033), active caspase-3 expression in marrow showed a strong correlation (r=0.764; p=0.001) to peripheral blood mononuclear cells in ALL and a medium correlation (r=0.594; p=0.042) in AML. The expression of the active caspase-3 in ALL patients was lower in complete remission patients compared to the non-complete remission patients. Regarding to this study it is recommended to measure the active caspase-3 along with molecules integrating in apoptosis signaling pathways such as cytochrome-c and in the formation of apoptosome.

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