CCAAT/enhancer binding protein epsilon is critical for effective neutrophil-mediated response to inflammatory challenge.
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.[1]References
- CCAAT/enhancer binding protein epsilon is critical for effective neutrophil-mediated response to inflammatory challenge. Lekstrom-Himes, J., Xanthopoulos, K.G. Blood (1999) [Pubmed]
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