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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1794-1801
PHAGOCYTES
Macrophage functional maturation and cytokine production are
impaired in C/EBP -deficient mice
Sigal Tavor,
Peter T. Vuong,
Dorothy J. Park,
Adrian F. Gombart,
Arthur H. Cohen, and
H. Phillip Koeffler
From the Division of Hematology/Oncology and the
Department of Pathology, Cedars-Sinai Medical Center, UCLA School of
Medicine, Los Angeles, CA.
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
expression is restricted to granulocytes, macrophages, and lymphocytes.
C/EBP is highly conserved between human and rodents and is essential
for terminal granulopoiesis in both species. To study the role that
C/EBP plays in macrophages, wild-type and C/EBP-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/ 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/ 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 gene as an important transcription factor
required for normal function and development of macrophages.
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