Is suppression of apoptosis a new therapeutic target in sepsis?

M Harjai1, J Bogra, M Kohli

  • 1Department of Anesthesilogy, Chhatrapati Shahuji Maharaj Medical University, Lucknow, Uttar Pradesh, India. mamtaharjaidoctor@yahoo.co.in

Insights

Sepsis is a major cause of death. Blocking immune cell apoptosis, programmed cell death, may offer a novel therapeutic strategy to improve sepsis survival rates.

Area of Science:

  • Critical care medicine
  • Immunology
  • Molecular biology

Background:

  • Sepsis is a leading cause of mortality in critically ill patients.
  • Few effective therapies exist to reduce sepsis-related death and illness.
  • Apoptosis (programmed cell death) is a key cell death mechanism in sepsis.

Purpose of the Study:

  • To review the role of immune cell apoptosis in sepsis pathophysiology.
  • To propose targeting apoptosis pathways as a potential sepsis therapy.

Main Methods:

  • Review of existing literature on sepsis and apoptosis.
  • Discussion of various apoptosis inhibition strategies.

Main Results:

  • Immune cell apoptosis significantly contributes to sepsis progression.
  • Preventing apoptosis improved survival in animal sepsis models.

Conclusions:

  • Targeting cell-signaling pathways that induce apoptosis is a promising therapeutic approach for sepsis.
  • Methods like Fas receptor inhibitors, caspase inhibitors, and gene-based therapies warrant further investigation.

Related Concept Videos

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 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...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
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...