| First Author | Lekstrom-Himes J | Year | 1999 |
| Journal | Blood | Volume | 93 |
| Issue | 9 | Pages | 3096-105 |
| PubMed ID | 10216107 | Mgi Jnum | J:54573 |
| Mgi Id | MGI:1336504 | Doi | 10.1182/blood.v93.9.3096 |
| Citation | Lekstrom-Himes J, et al. (1999) CCAAT/enhancer binding protein epsilon is critical for effective neutrophil-mediated response to inflammatory challenge. Blood 93(9):3096-105 |
| abstractText | 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. |
