Limits...
Sepsis induces extensive autophagic vacuolization in hepatocytes: a clinical and laboratory-based study.

Watanabe E, Muenzer JT, Hawkins WG, Davis CG, Dixon DJ, McDunn JE, Brackett DJ, Lerner MR, Swanson PE, Hotchkiss RS - Lab. Invest. (2009)

Bottom Line: In rare instances, hepatocytes with autophagic vacuoles appeared to be unequivocally committed to death.In conclusion, hepatocyte autophagic vacuolization increases during sepsis and is associated with mitochondrial injury.However, it is not possible to determine whether the increase in autophagic vacuolization is an adaptive response or a harbinger of cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA.

ABSTRACT
Autophagy is the regulated process cells use to recycle nonessential, redundant, or inefficient components and is an adaptive response during times of stress. In addition to its function in enabling the cell to gain vital nutrients in times of stress, autophagy can also be involved in elimination of intracellular microorganisms, tumor suppression, and antigen presentation. Because of difficulty in diagnosing autophagy, few clinical studies have been performed. This study examined whether autophagy occurs in hepatocytes during sepsis. Electron microscopy (EM) was performed on liver samples obtained from both an observational clinical cohort of six septic patients and four control patients as well as liver specimens from mice with surgical sepsis (by cecal ligation and puncture) or sham operation. EM demonstrated increased autophagic vacuoles in septic vs nonseptic patients. Randomly selected fields (3000 microm(2)) from control and septic patients contained 1.2+/-1.5 vs 5.3+/-3.3 (mean+/-s.d.) complex lysosomal/autophagolysosomal structures per image respectively (P<0.001). In rare instances, hepatocytes with autophagic vacuoles appeared to be unequivocally committed to death. Membrane alterations (membrane vacuoles, invagination into adjacent organelles, and myelin figure-like changes) occur in a subpopulation of mitochondria in sepsis, but other hepatocyte organelles showed no consistent ultrastructural injury. Findings in murine sepsis paralleled those of patients, with 7.2+/-1.9 vs 38.7+/-3.9 lysosomal/autophagolysosomal structures in sham and septic mice, respectively (P=0.002). Quantitative RT-PCR demonstrated that sepsis induced the upregulation of select apoptosis and cytokine gene expression with minimal changes in the core autophagy genes in liver. In conclusion, hepatocyte autophagic vacuolization increases during sepsis and is associated with mitochondrial injury. However, it is not possible to determine whether the increase in autophagic vacuolization is an adaptive response or a harbinger of cell death.

Show MeSH

Related in: MedlinePlus

Figure 5a and 5b. Quantitation of messenger RNA in CD4 T and B cells at 8 and 18 hours after sepsis.Each gene shown is quantified relative to levels of sham operated mice. We show here that pro-and anti-inflammatory cytokines and SOCS3 expressions are increased early when compared to sham (*P<0.05, ** P<0.01) and decreased during the time course. Expression of the autophagic genes was not increased in septic versus sham mice at either 8 or 18 hrs after surgery.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3822608&req=5

Figure 5: Figure 5a and 5b. Quantitation of messenger RNA in CD4 T and B cells at 8 and 18 hours after sepsis.Each gene shown is quantified relative to levels of sham operated mice. We show here that pro-and anti-inflammatory cytokines and SOCS3 expressions are increased early when compared to sham (*P<0.05, ** P<0.01) and decreased during the time course. Expression of the autophagic genes was not increased in septic versus sham mice at either 8 or 18 hrs after surgery.


Sepsis induces extensive autophagic vacuolization in hepatocytes: a clinical and laboratory-based study.

Watanabe E, Muenzer JT, Hawkins WG, Davis CG, Dixon DJ, McDunn JE, Brackett DJ, Lerner MR, Swanson PE, Hotchkiss RS - Lab. Invest. (2009)

Figure 5a and 5b. Quantitation of messenger RNA in CD4 T and B cells at 8 and 18 hours after sepsis.Each gene shown is quantified relative to levels of sham operated mice. We show here that pro-and anti-inflammatory cytokines and SOCS3 expressions are increased early when compared to sham (*P<0.05, ** P<0.01) and decreased during the time course. Expression of the autophagic genes was not increased in septic versus sham mice at either 8 or 18 hrs after surgery.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822608&req=5

Figure 5: Figure 5a and 5b. Quantitation of messenger RNA in CD4 T and B cells at 8 and 18 hours after sepsis.Each gene shown is quantified relative to levels of sham operated mice. We show here that pro-and anti-inflammatory cytokines and SOCS3 expressions are increased early when compared to sham (*P<0.05, ** P<0.01) and decreased during the time course. Expression of the autophagic genes was not increased in septic versus sham mice at either 8 or 18 hrs after surgery.
Bottom Line: In rare instances, hepatocytes with autophagic vacuoles appeared to be unequivocally committed to death.In conclusion, hepatocyte autophagic vacuolization increases during sepsis and is associated with mitochondrial injury.However, it is not possible to determine whether the increase in autophagic vacuolization is an adaptive response or a harbinger of cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA.

ABSTRACT
Autophagy is the regulated process cells use to recycle nonessential, redundant, or inefficient components and is an adaptive response during times of stress. In addition to its function in enabling the cell to gain vital nutrients in times of stress, autophagy can also be involved in elimination of intracellular microorganisms, tumor suppression, and antigen presentation. Because of difficulty in diagnosing autophagy, few clinical studies have been performed. This study examined whether autophagy occurs in hepatocytes during sepsis. Electron microscopy (EM) was performed on liver samples obtained from both an observational clinical cohort of six septic patients and four control patients as well as liver specimens from mice with surgical sepsis (by cecal ligation and puncture) or sham operation. EM demonstrated increased autophagic vacuoles in septic vs nonseptic patients. Randomly selected fields (3000 microm(2)) from control and septic patients contained 1.2+/-1.5 vs 5.3+/-3.3 (mean+/-s.d.) complex lysosomal/autophagolysosomal structures per image respectively (P<0.001). In rare instances, hepatocytes with autophagic vacuoles appeared to be unequivocally committed to death. Membrane alterations (membrane vacuoles, invagination into adjacent organelles, and myelin figure-like changes) occur in a subpopulation of mitochondria in sepsis, but other hepatocyte organelles showed no consistent ultrastructural injury. Findings in murine sepsis paralleled those of patients, with 7.2+/-1.9 vs 38.7+/-3.9 lysosomal/autophagolysosomal structures in sham and septic mice, respectively (P=0.002). Quantitative RT-PCR demonstrated that sepsis induced the upregulation of select apoptosis and cytokine gene expression with minimal changes in the core autophagy genes in liver. In conclusion, hepatocyte autophagic vacuolization increases during sepsis and is associated with mitochondrial injury. However, it is not possible to determine whether the increase in autophagic vacuolization is an adaptive response or a harbinger of cell death.

Show MeSH
Related in: MedlinePlus