In:
Blood, American Society of Hematology, Vol. 93, No. 9 ( 1999-05-01), p. 3096-3105
Abstract:
Targeted mutation of CCAAT/enhancer binding protein (C/EBP) ɛ in mice results in early death, primarily due to spontaneous infection with Pseudomonas aeruginosa. Functional analysis of C/EBPɛ-deficient neutrophils, in an in vivo model of peritoneal inflammation, shows multiple defects. Reduction of phagocytotic killing by C/EBPɛ-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/EBPɛ-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- (TNF-) expression by C/EBPɛ-deficient neutrophils. Additionally, TNF- expression is increased in nonactivated, circulating C/EBPɛ-deficient neutrophils. Overall, C/EBPɛ-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/EBPɛ-deficient mouse model and the human disease, specific granule deficiency, will be discussed.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood.V93.9.3096.409k09_3096_3105
Language:
English
Publisher:
American Society of Hematology
Publication Date:
1999
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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