PMID- 10216107
OWN - NLM
STAT- MEDLINE
DCOM- 19990518
LR  - 20081121
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 9
DP  - 1999 May 1
TI  - CCAAT/enhancer binding protein epsilon is critical for effective
      neutrophil-mediated response to inflammatory challenge.
PG  - 3096-105
AB  - Targeted mutation of CCAAT/enhancer binding protein (C/EBP) epsilon in mice
      results in early death, primarily due to spontaneous infection with Pseudomonas
      aeruginosa. Functional analysis of C/EBPepsilon-deficient neutrophils, in an in
      vivo model of peritoneal inflammation, shows multiple defects. Reduction of
      phagocytotic killing by C/EBPepsilon-deficient neutrophils is a result of
      decreased uptake of opsonized bacteria as well as little to no expression of
      secondary granule proteins. Abnormalities in neutrophil migration detected in a
      chemical peritonitis model are likely secondary to abnormal CD11b integrin and
      L-selectin expression on C/EBPepsilon-deficient neutrophils. Alterations in
      neutrophil cytokine expression in response to inflammation show decreased levels 
      of interleukin-1 receptor antagonist (IL-1Ra) and increased levels of tumor
      necrosis factor-alpha (TNF-alpha) expression by C/EBPepsilon-deficient
      neutrophils. Additionally, TNF-alpha expression is increased in nonactivated,
      circulating C/EBPepsilon-deficient neutrophils. Overall, C/EBPepsilon-deficient
      neutrophils are severely functionally impaired, evoking an abnormal
      microenvironment, which may contribute to the loss of normal responses to
      inflammatory stimuli. Similarities between the C/EBPepsilon-deficient mouse model
      and the human disease, specific granule deficiency, will be discussed.
FAU - Lekstrom-Himes, J
AU  - Lekstrom-Himes J
AD  - Clinical Gene Therapy Branch, National Human Genome Research Institute, National 
      Institutes of Health, Bethesda, MD, USA. jlekstrom@atlas.niaid.nih.gov
FAU - Xanthopoulos, K G
AU  - Xanthopoulos KG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (IL1RN protein, human)
RN  - 0 (Il1rn protein, mouse)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Thioglycolates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126880-86-2 (L-Selectin)
SB  - AIM
SB  - IM
MH  - Animals
MH  - CCAAT-Enhancer-Binding Proteins
MH  - Chemotaxis, Leukocyte/drug effects/*physiology
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - *Enhancer Elements, Genetic
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation/blood/immunology
MH  - Interleukin 1 Receptor Antagonist Protein
MH  - L-Selectin/genetics
MH  - Macrophage-1 Antigen/genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Neutrophils/immunology/*physiology
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Peritoneal Cavity
MH  - *Phagocytosis
MH  - Sialoglycoproteins/genetics
MH  - Thioglycolates/pharmacology
MH  - Tumor Necrosis Factor-alpha/genetics
EDAT- 1999/04/27 00:00
MHDA- 1999/04/27 00:01
CRDT- 1999/04/27 00:00
PHST- 1999/04/27 00:00 [pubmed]
PHST- 1999/04/27 00:01 [medline]
PHST- 1999/04/27 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 May 1;93(9):3096-105.