Macrophage functional maturation and cytokine production are impaired in C/EBP epsilon-deficient mice.
Members of the CCAAT/enhancer-binding protein (C/EBP) family are involved in the regulation of cellular differentiation and function of many tissues. Unlike the other members of the family, C/EBP epsilon expression is restricted to granulocytes, macrophages, and lymphocytes. C/EBP epsilon is highly conserved between human and rodents and is essential for terminal granulopoiesis in both species. To study the role that C/EBP epsilon plays in macrophages, wild-type and C/EBP epsilon-deficient (-/-) murine macrophages obtained from thioglycollate-elicited peritoneal lavages and differentiated bone marrow cells were compared. Although macrophage development occurred in both types of mice, the C/EBP epsilon -/- cells had a lower expression of macrophage markers and a morphologic and ultrastructural appearance of immaturity. Phagocytic function, measured by calculating the percentage of internalized opsonized fluorescein isothiocyanate (FITC)-labeled yeast, was significantly impaired in the C/EBP epsilon -/- macrophages compared with their wild-type counterparts. Furthermore, the differential expression of 26 macrophage-specific genes between wild-type and C/EBP-/- mice was analyzed. A subset of genes involved in differentiation, immune, and inflammatory responses was found down-regulated in the C/EBP-/- macrophages. Taken together, this study implicates the C/EBP epsilon gene as an important transcription factor required for normal function and development of macrophages.
Tavor
Sigal
S
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90095, USA. koeffler@cshs.org
Vuong
Peter T
PT
Park
Dorothy J
DJ
Gombart
Adrian F
AF
Cohen
Arthur H
AH
Koeffler
H Phillip
HP
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000187:drug effects; D013864:Thioglycolates
D022762:CCAAT-Enhancer-Binding Proteins; C489468:Cebpe protein, mouse; D016207:Cytokines; D013864:Thioglycolates; C070790:CEBPE protein, human