期刊
IMMUNOLOGY AND CELL BIOLOGY
卷 90, 期 10, 页码 925-934出版社
WILEY
DOI: 10.1038/icb.2012.32
关键词
rodent; endotoxin shock; inflammation; infection; sepsis; monocytes/macrophages
资金
- East Tennessee State University College of Medicine
Effective treatment of the acute systemic inflammatory response associated with sepsis is lacking, but likely will require new ways to rebalance dysregulated immune responses. One challenge is that human sepsis often is diagnosed too late to reduce the hyperinflammation of early sepsis. Another is that the sequential response to sepsis inflammation rapidly generates an adaptive and immunosuppressive state, which by epigenetic imprint may last for months or years. Emerging data support that the immunosuppressive phase of sepsis can both directly reprogram gene expression of circulating and tissue cells, and disrupt development and differentiation of myeloid precursor cells into competent immunocytes. We recently reported that adoptive transfer of bone marrow CD34+ cells into mice after sepsis induction by cecal ligation and puncture significantly improves late-sepsis survival by enhancing bacterial clearance through improved neutrophil and macrophage phagocytosis. That study, however, did not examine whether CD34(+) transfer can modify noninfectious acute systemic inflammatory responses. Here, we report that CD34(+) cell transfer mice that have survived late sepsis also resist lethal lipopolysaccharide (LPS)-induced inflammatory shock (88% lived vs 0% of naive mice). The CD34(+) cell-recipient survivor mice administered LPS had globally reduced levels of circulating inflammatory mediators compared with naive mice, but their peritoneal and bone marrow-derived macrophages (BMDMs), unlike those from naive mice, remained LPS responsive ex vivo. We further found that CD34(+) cell transfer into LPS-challenged naive mice had diminished immunosuppression, as assessed by ex vivo responses of peritoneal and BMDMs to LPS challenge. We conclude that CD34(+) cell adoptive transfer rebalances dysregulated immune responses associated with sepsis and endotoxin shock. Immunology and Cell Biology (2012) 90, 925-934; doi: 10.1038/icb.2012.32; published online 26 June 2012
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