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Down-modulation of CD4 antigen during programmed cell death in U937 cells
W Malorni1, R Rivabene, M T Santini
1Department of Ultrastructures, Istituto Superiore di Sanità, Roma, Italy.
FEBS Letters
|December 27, 1993
Summary
Programmed cell death (PCD) in U937 cells, induced by tumor necrosis factor (TNF) and cycloheximide, alters CD4 molecule expression. This modification during apoptosis may influence human immunodeficiency virus (HIV) entry.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Programmed cell death (PCD) is an active cell suicide process distinct from necrosis.
- Acquired immunodeficiency syndrome (AIDS) pathogenesis may involve PCD.
- Human immunodeficiency virus (HIV) entry into cells is mediated by the CD4 molecule.
Purpose of the Study:
- To investigate the relationship between tumor necrosis factor (TNF)-induced PCD and CD4 surface molecule expression.
- To explore the role of cell death pathways in modulating HIV entry mechanisms.
Main Methods:
- U937 myelomonocytic cells were exposed to TNF and cycloheximide.
- Changes in CD4 surface molecule expression were analyzed.
- Apoptosis and necrosis were differentiated based on cellular morphology and molecular markers.
Main Results:
- Cycloheximide facilitates TNF-mediated PCD in U937 cells via a short-term program.
- TNF-induced PCD leads to the internalization of CD4 surface molecules in apoptotic cells.
- CD4 molecule internalization was not observed in cells undergoing necrosis.
Conclusions:
- Alterations in surface molecule expression, specifically CD4 internalization, are associated with the progression of apoptosis.
- These PCD-associated changes in CD4 expression may play a role in HIV's ability to enter cells.
- Understanding these mechanisms could provide insights into AIDS pathogenesis and viral entry.