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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2847-2854
Monocytes express high amounts of Notch and undergo cytokine
specific apoptosis following interaction with the Notch ligand, Delta-1
Kohshi Ohishi,
Barbara Varnum-Finney,
David Flowers,
Claudio Anasetti,
David Myerson, and
Irwin D. Bernstein
From the Clinical Research Division, Fred Hutchinson Cancer Research
Center, and the Departments of Pediatrics, Medicine, and Pathology, the
University of Washington, Seattle, WA.
Notch signaling has been shown to play a key role in cell fate
decisions in numerous developmental systems. Using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we reported the
expression of human Notch-1 in CD34+ progenitors. In this study, we
evaluated the expression of human Notch-1 and Notch-2 protein by
hematopoietic cells. In immunofluoresence study, we detected low
amounts of Notch-1 and Notch-2 protein in both CD34+ and
CD34+Lin cells, high amounts in CD14+ monocytes as well as B and
T cells, but no expression in CD15+ granulocytes. We further found
that an immobilized truncated form of the Notch ligand, Delta-1,
induced apoptosis in monocytes in the presence of macrophage colony-stimulating factor (M-CSF), but not granulocyte-macrophage colony-stimulating factor (GM-CSF). The widespread expressions of Notch
proteins suggest multiple functions for this receptor during
hematopoiesis. These studies further indicate a novel role for Notch in
regulating monocyte survival.
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