Book contents
- Frontmatter
- Contents
- Contributors
- Part I General Principles of Cell Death
- Part II Cell Death in Tissues and Organs
- 11 Cell Death in Nervous System Development and Neurological Disease
- 12 Role of Programmed Cell Death in Neurodegenerative Disease
- 13 Implications of Nitrosative Stress-Induced Protein Misfolding in Neurodegeneration
- 14 Mitochondrial Mechanisms of Neural Cell Death in Cerebral Ischemia
- 15 Cell Death in Spinal Cord Injury – An Evolving Taxonomy with Therapeutic Promise
- 16 Apoptosis and Homeostasis in the Eye
- 17 Cell Death in the Inner Ear
- 18 Cell Death in the Olfactory System
- 19 Contribution of Apoptosis to Physiologic Remodeling of the Endocrine Pancreas and Pathophysiology of Diabetes
- 20 Apoptosis in the Physiology and Diseases of the Respiratory Tract
- 21 Regulation of Cell Death in the Gastrointestinal Tract
- 22 Apoptosis in the Kidney
- 23 Physiologic and Pathological Cell Death in the Mammary Gland
- 24 Therapeutic Targeting Apoptosis in Female Reproductive Biology
- 25 Apoptotic Signaling in Male Germ Cells
- 26 Cell Death in the Cardiovascular System
- 27 Cell Death Regulation in Muscle
- 28 Cell Death in the Skin
- 29 Apoptosis and Cell Survival in the Immune System
- 30 Cell Death Regulation in the Hematopoietic System
- 31 Apoptotic Cell Death in Sepsis
- 32 Host–Pathogen Interactions
- Part III Cell Death in Nonmammalian Organisms
- Plate section
- References
31 - Apoptotic Cell Death in Sepsis
from Part II - Cell Death in Tissues and Organs
Published online by Cambridge University Press: 07 September 2011
Book contents
- Frontmatter
- Contents
- Contributors
- Part I General Principles of Cell Death
- Part II Cell Death in Tissues and Organs
- 11 Cell Death in Nervous System Development and Neurological Disease
- 12 Role of Programmed Cell Death in Neurodegenerative Disease
- 13 Implications of Nitrosative Stress-Induced Protein Misfolding in Neurodegeneration
- 14 Mitochondrial Mechanisms of Neural Cell Death in Cerebral Ischemia
- 15 Cell Death in Spinal Cord Injury – An Evolving Taxonomy with Therapeutic Promise
- 16 Apoptosis and Homeostasis in the Eye
- 17 Cell Death in the Inner Ear
- 18 Cell Death in the Olfactory System
- 19 Contribution of Apoptosis to Physiologic Remodeling of the Endocrine Pancreas and Pathophysiology of Diabetes
- 20 Apoptosis in the Physiology and Diseases of the Respiratory Tract
- 21 Regulation of Cell Death in the Gastrointestinal Tract
- 22 Apoptosis in the Kidney
- 23 Physiologic and Pathological Cell Death in the Mammary Gland
- 24 Therapeutic Targeting Apoptosis in Female Reproductive Biology
- 25 Apoptotic Signaling in Male Germ Cells
- 26 Cell Death in the Cardiovascular System
- 27 Cell Death Regulation in Muscle
- 28 Cell Death in the Skin
- 29 Apoptosis and Cell Survival in the Immune System
- 30 Cell Death Regulation in the Hematopoietic System
- 31 Apoptotic Cell Death in Sepsis
- 32 Host–Pathogen Interactions
- Part III Cell Death in Nonmammalian Organisms
- Plate section
- References
Summary
Introduction
More than 210,000 people die from sepsis in the United States each year, with an annual cost of more than 16 billion dollars. Despite continued advances in treatment and prevention, sepsis is a growing problem, with a significant mortality rate of 28% to 50%. In the past, death from sepsis was thought be due to uncontrolled inflammation, and as a result, numerous anti-inflammatory therapeutics were developed. Uncontrolled inflammation leading to death may be true in sepsis due to certain types of pathogens (e.g., Neisseria meningitides, Clostridium perfringens) and in these patients anti-inflammatory therapies may help. However, large-scale clinical trials of anti-inflammatory therapies in septic patients have failed to reduce patient mortality. Recent research into the host's immune response in sepsis has led to a fundamental change in the way clinicians and researchers think about this disease. After an initial hyper-inflammatory phase, septic patients may descend into a period of prolonged immune suppression, and it is during this period that the majority of patients die. Death usually occurs from multiorgan system failure brought on by the host's inability to clear the primary infection or from a second opportunistic or nosocomial infection. One important hallmark of sepsis is widespread cell death in multiple organ systems due to both apoptosis and necrosis. This chapter reviews the cell types that undergo apoptosis and necrosis, the known inciting factors and mechanisms of cell death, and the impact of sepsis-induced apoptosis on morbidity and mortality, especially focusing on the importance of the lymphocyte.
- Type
- Chapter
- Information
- ApoptosisPhysiology and Pathology, pp. 363 - 371Publisher: Cambridge University PressPrint publication year: 2011
References
, , and . Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med, 1997. 25(7): p. 1095–100.
, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med, 2001. 29(7): p. 1303–10.
, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 1992. 101(6): p. 1644–55.
, et al. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med, 2007. 35(5): p. 1244–50.
, et al. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. N Engl J Med, 1988. 319(7): p. 397–400.
and . The pathophysiology and treatment of sepsis. N Engl J Med, 2003. 348(2): p. 138–50.
, et al. Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med, 2006. 32(8): p. 1175–83.
, , and . Sepsis syndromes: understanding the role of innate and acquired immunity. Shock, 2001. 16(2): p. 83–96.
Pathophysiology of sepsis. Am J Pathol, 2007. 170(5): p. 1435–44.
, et al. Delayed hypersensitivity: indicator of acquired failure of host defenses in sepsis and trauma. Ann Surg, 1977. 186(3): p. 241–50.
, et al. Selective defects of T lymphocyte function in patients with lethal intraabdominal infection. Am J Surg, 1999. 178(4): p. 288–92.
, , and . The effects of injury on the adaptive immune response. Shock, 1999. 11(3): p. 153–9.
, et al. The contribution of CD4+CD25+T-regulatory-cells to immune suppression in sepsis. Shock, 2007. 27(3): p. 251–7.
, et al. Marked elevation of human circulating CD4+CD25+regulatory T cells in sepsis-induced immunoparalysis. Crit Care Med, 2003. 31(7): p. 2068–71.
, et al. Interferon-gamma attenuates hemorrhage-induced suppression of macrophage and splenocyte functions and decreases susceptibility to sepsis. Surgery, 1992. 111(2): p. 177–87.
, et al. Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat Med, 1997. 3(6): p. 678–81.
, et al. Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients. J Lab Clin Med, 2000. 135(2): p. 153–60.
, et al. Predictive value of monocyte histocompatibility leukocyte antigen-DR expression and plasma interleukin-4 and -10 levels in critically ill patients with sepsis. Shock, 2003. 20(1): p. 1–4.
, et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med, 1999. 27(7): p. 1230–51.
, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol, 2001. 166(11): p. 6952–63.
, et al. Depletion of dendritic cells, but not macrophages, in patients with sepsis. J Immunol, 2002. 168(5): p. 2493–500.
, et al. Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure. J Immunol, 2005. 174(6): p. 3765–72.
, et al. Spleen depletion in neonatal sepsis and chorioamnionitis. Am J Clin Pathol, 2004. 122(5): p. 765–71.
, et al. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock, 2002. 18(6): p. 487–94.
, et al. Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis. Crit Care, 2008. 12(5): p. R128.
and . Intestinal crosstalk: a new paradigm for understanding the gut as the “motor” of critical illness. Shock, 2007. 28(4): p. 384–93.
Animal models of sepsis and shock: a review and lessons learned. Shock, 1998. 9(1): p. 1–11.
, et al. Cecal ligation and puncture. Shock, 2005. 24 Suppl 1: p. 52–7.
and . Animal models of human pneumonia. Am J Physiol Lung Cell Mol Physiol, 2008. 294(3): p. L387–98.
, et al. Pneumonia after cecal ligation and puncture: a clinically relevant “two-hit” model of sepsis. Shock, 2006. 26(6): p. 565–70.
and . Cell death control in lymphocytes. Adv Immunol, 2000. 76: p. 179–226.
and . Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more. Annu Rev Immunol, 2003. 21: p. 71–105.
The role of BH3-only proteins in the immune system. Nat Rev Immunol, 2005. 5(3): p. 189–200.
, et al. Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol, 1999. 162(7): p. 4148–56.
, et al. Prevention of lymphocyte cell death in sepsis improves survival in mice. Proc Natl Acad Sci U S A, 1999. 96(25): p. 14541–6.
, et al. Inhibition of intestinal epithelial apoptosis and survival in a murine model of pneumonia-induced sepsis. JAMA, 2002. 287(13): p. 1716–21.
, et al. Sepsis from Pseudomonas aeruginosa pneumonia decreases intestinal proliferation and induces gut epithelial cell cycle arrest. Crit Care Med, 2003. 31(6): p. 1630–7.
, et al. Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways. J Immunol, 2005. 174(8): p. 5110–8.
, et al. Multiple triggers of cell death in sepsis: death receptor and mitochondrial-mediated apoptosis. FASEB J, 2007. 21(3): p. 708–19.
, et al. Inhibition of Fas/Fas ligand signaling improves septic survival: differential effects on macrophage apoptotic and functional capacity. J Leukoc Biol, 2003. 74(3): p. 344–51.
, et al. Increased inducible apoptosis in CD4+ T lymphocytes during polymicrobial sepsis is mediated by Fas ligand and not endotoxin. Immunology, 1999. 97(1): p. 45–55.
, et al. Deletion of MyD88 markedly attenuates sepsis-induced T and B lymphocyte apoptosis but worsens survival. J Leukoc Biol, 2008. 83(4): p. 1009–18.
, et al. Over-expression of Bcl-2 provides protection in septic mice by a trans effect. J Immunol, 2003. 171(6): p. 3136–41.
and . Controlling the cell death mediators Bax and Bak: puzzles and conundrums. Cell Cycle, 2008. 7(1): p. 39–44.
, et al. Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature, 1999. 400(6747): p. 886–91.
Death-defying immunity: do apoptotic cells influence antigen processing and presentation? Nat Rev Immunol, 2004. 4(3): p. 223–31.
, et al. Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis. Proc Natl Acad Sci U S A, 2003. 100(11): p. 6724–9.
, et al. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat Immunol, 2000. 1(6): p. 496–501.
, et al. Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion. Cell Death Differ, 2006. 13(1): p. 41–52.
and . Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis. Nat Cell Biol, 2003. 5(1): p. 28–37.
and . TAT transduction: the molecular mechanism and therapeutic prospects. Trends Mol Med, 2007. 13(10): p. 443–8.
, et al. BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death. Proc Natl Acad Sci U S A, 2000. 97(7): p. 3100–5.
, et al. BH4-domain peptide from Bcl-xL exerts anti-apoptotic activity in vivo. Oncogene, 2003. 22(52): p. 8432–40.
, et al. Calpain and mitochondria in ischemia/reperfusion injury. J Biol Chem, 2002. 277(32): p. 29181–6.
, et al. Anti-apoptotic peptides protect against radiation-induced cell death. Biochem Biophys Res Commun, 2007. 355(2): p. 501–7.
, et al. TAT-BH4 and TAT-Bcl-xL peptides protect against sepsis-induced lymphocyte apoptosis in vivo. J Immunol, 2006. 176(9): p. 5471–7.
, et al. In vivo delivery of caspase-8 or Fas siRNA improves the survival of septic mice. Blood, 2005. 106(7): p. 2295–301.
, et al. Bim siRNA decreases lymphocyte apoptosis and improves survival in sepsis. Shock, 2008. 30(2): p. 127–34.
, et al. Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proc Natl Acad Sci U S A, 2007. 104(14): p. 5715–21.
, et al. Targeted delivery of siRNA to cell death proteins in sepsis. Shock, 2008. 32(2): p. 131–9.
, et al. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol, 2005. 23(6): p. 709–17.
, et al. Identification of novel superior polycationic vectors for gene delivery by high-throughput synthesis and screening of a combinatorial library. Pharm Res, 2007. 24(8): p. 1564–71.
, et al. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat Biotechnol, 2008. 26(5): p. 561–9.
, et al. Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. Nat Immunol, 2003. 4(10): p. 1016–22.
, et al. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis. J Immunol, 2010. 184(7):p. 3768–79.
, et al. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis. J Immunolol, 2010. 184(3): p. 1401–9.
, et al. Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis. J Leukoc Biol, 2010. 88(2): p. 233–40.