Programmed Cell Death and Apoptosis in Lymphocyte Development and Function

CHEST Journal ◽  
1993 ◽  
Vol 103 (2) ◽  
pp. 99S-101S ◽  
Author(s):  
J.John Cohen
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Lymphocyte Development ◽  
And Function

scholarly journals Programmed Cell Death-1 Receptor (PD-1)-Mediated Regulation of Innate Lymphoid Cells

2019 ◽  
Vol 20 (11) ◽  
pp. 2836 ◽  
Author(s):  
Grace Mallett ◽  
Arian Laurence ◽  
Shoba Amarnath
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Cell Surface Receptor ◽  
Programmed Cell Death 1 ◽  
Surface Receptor ◽  
A Cell ◽  
And Function

Programmed cell death-1 (PD-1) is a cell surface receptor that dampens adaptive immune responses. PD-1 is activated by the engagement of its ligands PDL-1 or PDL-2. This results in the inhibition of T cell proliferation, differentiation, cytokine secretion, and cytolytic function. Although a great deal is known about PD-1 mediated regulation of CD4+ and CD8+ T cells, its expression and function in innate lymphoid cells (ILCs) are yet to be fully deciphered. This review summarizes the role of PD-1 in (1) modulating ILC development, (2) ILC function, and (3) PD-1 signaling in ILC. Finally, we explore how PD-1 based immunotherapies may be beneficial in boosting ILC responses in cancer, infections, and other immune-related disorders.

scholarly journals Expression and function of Fas (APO-1/CD95) in patient myeloma cells and myeloma cell lines

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3566-3576 ◽  
Author(s):  
JJ Westendorf ◽  
JM Lammert ◽  
DF Jelinek
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Lines ◽  
Protective Factor ◽  
Plasma Cells ◽  
Myeloma Cell ◽  
Color Flow ◽  
Fas Antigen ◽  
Myeloma Cells ◽  
And Function

Cross-linkage of the Fas antigen induces programmed cell death in many normal and malignant lymphoid cells by a process known as apoptosis. In this study, we examined the sensitivity of myeloma cell lines and patient plasma cells to a cytolytic anti-Fas monoclonal antibody (MoAb). Eight of 10 myeloma cell lines were induced to undergo programmed cell death by anti-Fas MoAb as determined by DNA fragmentation and morphologic changes. Of the two myeloma cell lines that were resistant to anti-Fas treatment, one did not express the Fas antigen. Only the U266 cell line expressed Fas, but was not killed by the anti0Fas MoAb. To extend these studies, we have examined the expression and function of Fas in freshly isolated CD38hiCD45neg-int plasma cells from patients with multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and primary amyloidosis (AL). By three-color flow cytometry, we found Fas expression in CD38hiCD45neg-int plasma cells from all patient groups to be variable, as Fas was expressed in 15 of 28 MM, 3 of 6 MGUS, and 2 of 7 AL patients. In morphologic studies of apoptosis, Fas-positive myeloma cells in patient bone marrow mononuclear cell (MNC) cultures appeared to be resistant to anti-Fas-mediated apoptosis. By contrast, purified myeloma cells from the same patient were sensitive to anti-Fas treatment, suggesting the presence of a protective factor(s) in unseparated MNC cultures that may inhibit Fas-induced apoptosis of plasma cells. Of interest, serum from normal individuals and myeloma patients also protected myeloma cell lines from undergoing Fas-mediated apoptosis. These studies show that Fas expression in myeloma cell lines and CD38hiCD45neg-int patient plasma cells is variable and may reflect a variance in the maturation status of the various plasma cell populations. Moreover, Fas-mediated killing of patient cells and myeloma cell lines was also variable, which may be influenced, in part, by the presence of a soluble protective factor.

scholarly journals Calpain inhibition preserves myocardial structure and function following myocardial infarction

2009 ◽  
Vol 297 (5) ◽  
pp. H1744-H1751 ◽  
Author(s):  
Santhosh K. Mani ◽  
Sundaravadivel Balasubramanian ◽  
Juozas A. Zavadzkas ◽  
Laura B. Jeffords ◽  
William T. Rivers ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Left Ventricular ◽  
Structure And Function ◽  
Left Ventricular Ejection ◽  
Tunel Staining ◽  
Ventricular Ejection Fraction ◽  
Myocardial Structure ◽  
And Function

Cardiac pathology, such as myocardial infarction (MI), activates intracellular proteases that often trigger programmed cell death and contribute to maladaptive changes in myocardial structure and function. To test whether inhibition of calpain, a Ca2+-dependent cysteine protease, would prevent these changes, we used a mouse MI model. Calpeptin, an aldehydic inhibitor of calpain, was intravenously administered at 0.5 mg/kg body wt before MI induction and then at the same dose subcutaneously once per day. Both calpeptin-treated ( n = 6) and untreated ( n = 6) MI mice were used to study changes in myocardial structure and function after 4 days of MI, where end-diastolic volume (EDV) and left ventricular ejection fraction (EF) were measured by echocardiography. Calpain activation and programmed cell death were measured by immunohistochemistry, Western blotting, and TdT-mediated dUTP nick-end labeling (TUNEL). In MI mice, calpeptin treatment resulted in a significant improvement in EF [EF decreased from 67 ± 2% pre-MI to 30 ± 4% with MI only vs. 41 ± 2% with MI + calpeptin] and attenuated the increase in EDV [EDV increased from 42 ± 2 μl pre-MI to 73 ± 4 μl with MI only vs. 55 ± 4 μl with MI + calpeptin]. Furthermore, calpeptin treatment resulted in marked reduction in calpain- and caspase-3-associated changes and TUNEL staining. These studies indicate that calpain contributes to MI-induced alterations in myocardial structure and function and that it could be a potential therapeutic target in treating MI patients.

scholarly journals Changes in the Structure and Function of the Multicatalytic Proteinase (Proteasome) during Programmed Cell Death in the Intersegmental Muscles of the Hawkmoth, Manduca sexta

1995 ◽  
Vol 169 (2) ◽  
pp. 436-447 ◽  
Author(s):  
Margaret E.E. Jones ◽  
Marcy F. Haire ◽  
Peter-M. Kloetzel ◽  
Donald L. Mykles ◽  
Lawrence M. Schwartz
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Manduca Sexta ◽  
Structure And Function ◽  
Multicatalytic Proteinase ◽  
And Function

scholarly journals Extensive and diverse patterns of cell death sculpt neural networks in insects

2019 ◽  
Author(s):  
Sinziana Pop ◽  
Chin-Lin Chen ◽  
Connor J Sproston ◽  
Shu Kondo ◽  
Pavan Ramdya ◽  
...  
Keyword(s):  
Neural Networks ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Neural Activity ◽  
Structure And Function ◽  
Evolutionary Adaptation ◽  
Cell Numbers ◽  
The Many ◽  
And Function ◽  
Evolutionary Role

ABSTRACTChanges to the structure and function of neural networks are thought to underlie the evolutionary adaptation of animal behaviours. Among the many developmental phenomena that generate change programmed cell death appears to play a key role. We show that cell death occurs continuously throughout insect neurogenesis and happens soon after neurons are born. Focusing on two dipterans which have lost flight during evolution we reveal that reductions in populations of flight interneurons are likely caused by increased cell death during development.Mimicking an evolutionary role for increasing cell numbers, we artificially block programmed cell death in the medial neuroblast lineage in Drosophila melanogaster, which results in the production of ‘undead’ neurons with complex arborisations and distinct neurotransmitter identities. Activation of these ‘undead’ neurons and recordings of neural activity in behaving animals demonstrate that they are functional. Our findings suggest that the evolutionary modulation of death-based patterning could generate novel network configurations.

scholarly journals Conventional calpains and programmed cell death.

2011 ◽  
Vol 58 (3) ◽  
Author(s):  
Paulina Łopatniuk ◽  
Jacek M Witkowski
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
System Development ◽  
Cysteine Proteases ◽  
Drug Induced ◽  
Calcium Dependent ◽  
Immune System Development ◽  
Apoptotic Pathways ◽  
Induced Apoptosis ◽  
And Function

The evidence on the crucial role of a family of calcium-dependent cysteine proteases called calpains in programmed cell death is rich and still growing. However, understanding of the mechanisms of their functions in apoptosis is not full yet. Calpains have been implicated in both physiological and pathological cell death control, especially in various malignancies, but also in the immune system development and function. There is also growing evidence on calpain involvement in apoptosis execution in certain pathological conditions of the central nervous system, in cardiovascular diseases, etc. Understanding of the clinical significance of calpain activation pathways, after intense studies of the influence of calpain activity on drug-induced apoptosis, seems especially important lately, as calpains have become noticed as potential therapeutic targets. To allow pharmacological targeting of these enzymes, thorough knowledge of their patterns of activation and further interactions with already known apoptotic pathways is necessary. A comprehensive summary of both well established and recently obtained information in the field is an important step that may lead to future advances in the use of calpain-targeted agents in the clinic.

Activation of K+channels: an essential pathway in programmed cell death

2004 ◽  
Vol 286 (1) ◽  
pp. L49-L67 ◽  
Author(s):  
Carmelle V. Remillard ◽  
Jason X.-J. Yuan
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Apoptotic Cell ◽  
Malignant Cell ◽  
Pathological Feature ◽  
Inner Mitochondrial Membrane ◽  
Cell Shrinkage ◽  
Pulmonary Arterial ◽  
Medial Hypertrophy ◽  
And Function

Cell apoptosis and proliferation are two counterparts in sharing the responsibility for maintaining normal tissue homeostasis. In recent years, the process of the programmed cell death has gained much interest because of its influence on malignant cell growth and other pathological states. Apoptosis is characterized by a distinct series of morphological and biochemical changes that result in cell shrinkage, DNA breakdown, and, ultimately, phagocytic death. Diverse external and internal stimuli trigger apoptosis, and enhanced K+efflux has been shown to be an essential mediator of not only early apoptotic cell shrinkage, but also of downstream caspase activation and DNA fragmentation. The goal of this review is to discuss the role(s) played by K+transport or flux across the plasma membrane in the regulation of the apoptotic volume decrease and apoptosis. Attention has also been paid to the role of inner mitochondrial membrane ion transport in the regulation of mitochondrial permeability and apoptosis. We provide specific examples of how deregulation of the apoptotic process contributes to pulmonary arterial medial hypertrophy, a major pathological feature in patients with pulmonary arterial hypertension. Finally, we discuss the targeting of K+channels as a potential therapeutic tool in modulating apoptosis to maintain the balance between cell proliferation and cell death that is essential to the normal development and function of an organism.

scholarly journals From Cell Death to Regeneration: Rebuilding After Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Dylan J. Guerin ◽  
Cindy X. Kha ◽  
Kelly Ai-Sun Tseng
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Normal Development ◽  
Tissue Remodeling ◽  
Cell Number ◽  
The Body ◽  
Apoptosis Induction ◽  
New Knowledge ◽  
And Function

The ability to regrow lost or damaged tissues is widespread, but highly variable among animals. Understanding this variation remains a challenge in regeneration biology. Numerous studies from Hydra to mouse have shown that apoptosis acts as a potent and necessary mechanism in regeneration. Much is known about the involvement of apoptosis during normal development in regulating the number and type of cells in the body. In the context of regeneration, apoptosis also regulates cell number and proliferation in tissue remodeling. Apoptosis acts both early in the process to stimulate regeneration and later to regulate regenerative patterning. Multiple studies indicate that apoptosis acts as a signal to stimulate proliferation within the regenerative tissues, producing the cells needed for full regeneration. The conservation of apoptosis as a regenerative mechanism demonstrated across species highlights its importance and motivates the continued investigation of this important facet of programmed cell death. This review summarizes what is known about the roles of apoptosis during regeneration, and compares regenerative apoptosis with the mechanisms and function of apoptosis in development. Defining the complexity of regenerative apoptosis will contribute to new knowledge and perspectives for understanding mechanisms of apoptosis induction and regulation.

scholarly journals Combined cytotoxic chemotherapy and immunotherapy of cancer: modern times

NAR Cancer ◽  
2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Christian Bailly ◽  
Xavier Thuru ◽  
Bruno Quesnel
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Cells ◽  
Suppressor Cells ◽  
Cytotoxic Drugs ◽  
Immune Checkpoints ◽  
Microtubule Network ◽  
Modern Approach ◽  
Immunotherapy Of Cancer ◽  
And Function

Abstract Monoclonal antibodies targeting programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoints have improved the treatments of cancers. However, not all patients equally benefit from immunotherapy. The use of cytotoxic drugs is practically inevitable to treat advanced cancers and metastases. The repertoire of cytotoxics includes 80 products that principally target nucleic acids or the microtubule network in rapidly proliferating tumor cells. Paradoxically, many of these compounds tend to become essential to promote the activity of immunotherapy and to offer a sustained therapeutic effect. We have analyzed each cytotoxic drug with respect to effect on expression and function of PD-(L)1. The major cytotoxic drugs—carboplatin, cisplatin, cytarabine, dacarbazine, docetaxel, doxorubicin, ecteinascidin, etoposide, fluorouracil, gemcitabine, irinotecan, oxaliplatin, paclitaxel and pemetrexed—all have the capacity to upregulate PD-L1 expression on cancer cells (via the generation of danger signals) and to promote antitumor immunogenicity, via activation of cytotoxic T lymphocytes, maturation of antigen-presenting cells, depletion of immunosuppressive regulatory T cells and/or expansion of myeloid-derived suppressor cells. The use of ‘immunocompatible’ cytotoxic drugs combined with anti-PD-(L)1 antibodies is a modern approach, not only for increasing the direct killing of cancer cells, but also as a strategy to minimize the activation of immunosuppressive and cancer cell prosurvival program responses.

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