PMID- 22732898
OWN - NLM
STAT- MEDLINE
DCOM- 20130520
LR  - 20211021
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Linking)
VI  - 90
IP  - 10
DP  - 2012 Nov
TI  - Adoptive transfer of CD34(+) cells during murine sepsis rebalances macrophage 
      lipopolysaccharide responses.
PG  - 925-34
LID - 10.1038/icb.2012.32 [doi]
AB  - 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.
FAU - Brudecki, Laura
AU  - Brudecki L
AD  - Department of Internal Medicine, East Tennessee State University College of 
      Medicine, Johnson City, TN 37614, USA.
FAU - Ferguson, Donald A
AU  - Ferguson DA
FAU - McCall, Charles E
AU  - McCall CE
FAU - El Gazzar, Mohamed
AU  - El Gazzar M
LA  - eng
GR  - R01 AI079144/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120626
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Antigens, CD34)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - *Adoptive Transfer
MH  - Animals
MH  - Antigens, CD34/*immunology
MH  - Cecum/immunology/surgery
MH  - Cell Differentiation/immunology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/*immunology/microbiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Myeloid Cells/*immunology/*transplantation
MH  - Neutrophils/immunology/microbiology
MH  - Phagocytosis
MH  - Sepsis/*immunology/*therapy
EDAT- 2012/06/27 06:00
MHDA- 2013/05/22 06:00
CRDT- 2012/06/27 06:00
PHST- 2012/06/27 06:00 [entrez]
PHST- 2012/06/27 06:00 [pubmed]
PHST- 2013/05/22 06:00 [medline]
AID - icb201232 [pii]
AID - 10.1038/icb.2012.32 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2012 Nov;90(10):925-34. doi: 10.1038/icb.2012.32. Epub 2012 
      Jun 26.