Cathepsin‐cleaved Bid promotes apoptosis in human neutrophils via oxidative stress‐induced lysosomal membrane permeabilization

  title={Cathepsin‐cleaved Bid promotes apoptosis in human neutrophils via oxidative stress‐induced lysosomal membrane permeabilization},
  author={Robert Blomgran and Limin Zheng and Olle Stendahl},
  journal={Journal of Leukocyte Biology},
Lysosomal membrane permeabilization (LMP) is emerging as an important regulator of cell apoptosis. Human neutrophils are highly granulated phagocytes, which respond to pathogens by exhibiting increased production of reative oxygen species (ROS) and lysosomal degranulation. In a previous study, we observed that intracellular, nonphagosomal generation of ROS triggered by adherent bacteria induced ROS‐dependent neutrophil apoptosis, whereas intraphagosomal production of ROS during phagocytosis had… 

Subversion of a Lysosomal Pathway Regulating Neutrophil Apoptosis by a Major Bacterial Toxin, Pyocyanin1

This study investigated the mechanisms of pyocyanin-induced neutrophil apoptosis and described the first description of a bacterial toxin using a lysosomal cell death pathway, which may be a pathological pathway of cell death to which neutrophils are particularly susceptible, and could be therapeutically targeted to limit neutrophIL death and preserve host responses.

TNF&agr;-induced lysosomal membrane permeability is downstream of MOMP and triggered by caspase-mediated NDUFS1 cleavage and ROS formation

The novel finding that LMP induced by the addition of TNF&agr; plus cycloheximide (CHX), the release of lysosomal cathepsins and ROS formation do not occur upstream but downstream of MOMP and require the caspase-3-mediated cleavage of the p75 NDUFS1 subunit of respiratory complex I is presented.

Lysosomal membrane permeabilization in cell death

The regulation of LMP is perturbed in cancer cells, suggesting that specific strategies for LMP induction might lead to novel therapeutic avenues.

A Cardinal Role for Cathepsin D in Co-Ordinating the Host-Mediated Apoptosis of Macrophages and Killing of Pneumococci

It is shown that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis in pulmonary host defense and underscores the importance of apoptosis-associated microbial killing to macrophages function.

Cysteine Cathepsins Trigger Caspase-dependent Cell Death through Cleavage of Bid and Antiapoptotic Bcl-2 Homologues*

It is proposed that degradation of anti-apoptotic Bcl-2 family members by lysosomal cathepsins synergizes with cathepsypsin-mediated activation of Bid to trigger a mitochondrial pathway to apoptosis.

Regulation of apoptosis-associated lysosomal membrane permeabilization

A growing body of evidence suggests that LMP may be governed by several distinct mechanisms that are likely engaged in a death stimulus- and cell-type-dependent fashion, and factors contributing to permeabilization of the lysosomal membrane including reactive oxygen species, lysOSomal membrane lipid composition, proteases, p53, and Bcl-2 family proteins are described.

Anthrax Lethal Toxin Induced Lysosomal Membrane Permeabilization and Cytosolic Cathepsin Release Is Nlrp1b/Nalp1b-Dependent

A role for lysosomal membrane permeabilization in the cellular response to bacterial pathogens is revealed and a shared requirement for cytosolic relocalization of cathepsins in pyroptosis and pyronecrosis is demonstrated.

Constitutive neutrophil apoptosis: Mechanisms and regulation

The current understanding regarding the modulation of neutrophil apoptotic death by various extracellular stimuli such as proinflammatory cytokines, cell adhesion, phagocytosis, red blood cells, and platelets is summarized.



Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils

It is proposed that activated neutrophils use intracellularly formed H2O2 to commit suicide, and PMA nor ionomycin caused apoptosis in dimethyl sulfoxide‐differentiated HL‐60 cells, whereas H2 O2 induced apoptosis more efficiently in these cells than in neutrophil.

Mycobacterium tuberculosis Promotes Apoptosis in Human Neutrophils by Activating Caspase-3 and Altering Expression of Bax/Bcl-xL Via an Oxygen-Dependent Pathway1

The results indicate that infection with Mtb causes ROS-dependent alteration of Bax/Bcl-xL expression and activation of caspase-3, and thereby induces apoptosis in human neutrophils, which may represent an important host defense mechanism aimed at selective removal of infected cells at the inflamed site, which in turn aids the functional activities of local macrophages.

The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress

It is suggested that translocation of lysosomal proteases is an early event in NZ‐induced apoptosis and that the release and increased activity of cathepsin D allow this protease to exert an apoptosis‐mediating effect upstream of the caspase cascade.

Lysosomal and mitochondrial pathways in H2O2‐induced apoptosis of alveolar type II cells

The role of lysosomes as modulators of oxidant‐mediated AT II cell apoptosis using an in vitro model of H2O2‐stress is investigated and inhibition of cathepsin D prevented mitochondrial permeabilization and cythocrome c release suggesting that lysOSomal rupture precedes and is necessary for the activation of the mitochondrial pathway of cell death.

Oxidative stress, growth factor starvation and Fas activation may all cause apoptosis through lysosomal leak.

  • U. BrunkI. Svensson
  • Biology, Chemistry
    Redox report : communications in free radical research
  • 1999
The results indicate that lysosomal leakage/rupture precedes apoptosis in Jurkat cells regardless of the initiating agent, but that such rupture may occur through multiple mechanisms.

Elucidation of Molecular Events Leading to Neutrophil Apoptosis following Phagocytosis

These studies suggest that Mac-1-mediated phagocytosis promotes apoptosis through a caspase 8/3-dependent pathway that is modulated by NADPH oxidase-generated ROS and MAPK/ERK.

Lysosomal Protease Pathways to Apoptosis

Data suggest that Bid represents a sensor that allows cells to initiate apoptosis in response to widespread adventitious proteolysis, supported by the finding that cytosolic extracts from mice ablated in the bid gene are impaired in the ability to release cytochrome c in Response to lysosome extracts.

Cathepsin D Triggers Bax Activation, Resulting in Selective Apoptosis-inducing Factor (AIF) Relocation in T Lymphocytes Entering the Early Commitment Phase to Apoptosis*

A novel sequence of events in which Cat D triggers Bax activation, Bax induces the selective release of mitochondrial AIF, and the latter is responsible for the early apoptotic phenotype is defined.

Cathepsin B contributes to TNF-alpha-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c.

Caspase-mediated release of cat B from lysosomes enhances mitochondrial release of cytochrome c and subsequent caspase activation in TNF-alpha-treated hepatocytes.