Journal article
Extracellular Administration of BCL2 Protein Reduces Apoptosis and Improves Survival in a Murine Model of Sepsis
PloS one, v 6(2), pp e14729-e14729
24 Feb 2011
PMID: 21390214
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Severe sepsis and septic shock are major causes of morbidity and mortality worldwide. In experimental sepsis there is prominent apoptosis of various cell types, and genetic manipulation of death and survival pathways has been shown to modulate organ injury and survival.
Methodology/Principal Findings: We investigated the effect of extracellular administration of two anti-apoptotic members of the BCL2 (B-cell lymphoma 2) family of intracellular regulators of cell death in a murine model of sepsis induced by cecal ligation and puncture (CLP). We show that intraperitoneal injection of picomole range doses of recombinant human (rh) BCL2 or rhBCL2A1 protein markedly improved survival as assessed by surrogate markers of death. Treatment with rhBCL2 or rhBCL2A1 protein significantly reduced the number of apoptotic cells in the intestine and heart following CLP, and this was accompanied by increased expression of endogenous mouse BCL2 protein. Further, mice treated with rhBCL2A1 protein showed an increase in the total number of neutrophils in the peritoneum following CLP with reduced neutrophil apoptosis. Finally, although neither BCL2 nor BCL2A1 are a direct TLR2 ligand, TLR2-null mice were not protected by rhBCL2A1 protein, indicating that TLR2 signaling was required for the protective activity of extracellularly adminsitered BCL2A1 protein in vivo.
Conclusions/Significance: Treatment with rhBCL2A1 or rhBCL2 protein protects mice from sepsis by reducing apoptosis in multiple target tissues, demonstrating an unexpected, potent activity of extracellularly administered BCL2 BH4-domain proteins.
Metrics
Details
- Title
- Extracellular Administration of BCL2 Protein Reduces Apoptosis and Improves Survival in a Murine Model of Sepsis
- Creators
- Akiko Iwata - University of WashingtonR. Angelo de Claro - University of WashingtonVicki L. Morgan-Stevenson - University of WashingtonJoan C. Tupper - University of WashingtonBarbara R. Schwartz - University of WashingtonLi Liu - University of WashingtonXiaodong Zhu - University of WashingtonKatherine C. Jordan - University of WashingtonRobert K. Winn - University of WashingtonJohn M. Harlan - University of Washington
- Publication Details
- PloS one, v 6(2), pp e14729-e14729
- Publisher
- Public Library Science
- Number of pages
- 10
- Grant note
- R01GM071398 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) GM042686; GM071398 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000287761700007
- Scopus ID
- 2-s2.0-79952094321
- Other Identifier
- 991019415773404721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Immunology