Related Experiment Video

Updated: Jul 16, 2026

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

Multiple triggers of cell death in sepsis: death receptor and mitochondrial-mediated apoptosis

Katherine C Chang1, Jacqueline Unsinger, Christopher G Davis

  • 1Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|February 20, 2007
PubMed

Insights

Sepsis triggers lymphocyte apoptosis through multiple pathways. Targeting the Bim protein offered significant protection against this cell death and improved survival in mice.

Area of Science:

  • Immunology
  • Cell Biology
  • Pathophysiology

Background:

  • Lymphocyte apoptosis is critical in sepsis pathophysiology.
  • Understanding the pathways of lymphocyte apoptosis is key to developing treatments.

Purpose of the Study:

  • To investigate the roles of death receptor and mitochondrial pathways in sepsis-induced lymphocyte apoptosis.
  • To evaluate the therapeutic potential of targeting specific apoptosis-regulating proteins.

Main Methods:

  • Used genetically modified mice lacking key proteins in death receptor (FADD-DN, Bid-/-) and mitochondrial (Bim-/-, Puma-/-, Noxa-/-) pathways.
  • Assessed lymphocyte apoptosis, survival rates, and cytokine levels (IL-10, IL-6).
  • Performed adoptive transfer experiments using splenocytes from Bim-/- mice.

Main Results:

  • Defects in death receptor pathways (FADD-DN, Bid-/-) offered incomplete protection against lymphocyte apoptosis and increased survival.
  • Loss of Bim (Bim-/-) provided near-complete protection against lymphocyte apoptosis and improved survival, linked to reduced IL-10 and IL-6.
  • Mice lacking Puma or Noxa showed minimal protection.
  • Protection in Bim-/- mice was intrinsic to lymphocytes and associated with reduced pro-inflammatory cytokines.

Conclusions:

  • Sepsis involves multiple death stimuli, making single-target inhibition of apoptosis unlikely.
  • The Bim protein is a crucial mediator of sepsis-induced lymphocyte apoptosis.
  • Targeting proapoptotic proteins, potentially via siRNA, could be a therapeutic strategy for sepsis.

More Related Videos

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay05:52

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay

Published on: May 12, 2023

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...