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Tumor necrosis factor: receptors on hematopoietic cells
R Munker1, J DiPersio, H P Koeffler
1Department of Medicine, University of California Medical Center, Los Angeles.
Blood
|December 1, 1987
Summary
Tumor necrosis factor (TNF) receptors are present on myeloid cells, but their number doesn't predict TNF's cytotoxic effect. Significant biological impacts occur even with low receptor occupancy, indicating resistance isn't due to receptor absence.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Tumor necrosis factor (TNF) is a cytokine with cytotoxic and cytostatic properties against tumor cells.
- TNF also exerts diverse effects on normal cells, necessitating an understanding of its receptor interactions.
Purpose of the Study:
- To investigate the expression and characteristics of TNF receptors on normal and malignant human myeloid cells.
- To determine the relationship between TNF receptor number, affinity, and the cytotoxic activity of TNF on myeloid cell lines.
Main Methods:
- Quantification of high-affinity TNF receptors on various human myeloid cell lines and lymphocytes using radioligand binding assays.
- Assessment of TNF's cytotoxic/cytostatic effects on myeloid cell lines.
- Correlation analysis between receptor parameters and biological responses.
Main Results:
- Normal and malignant human myeloid cells express a single class of high-affinity TNF receptors.
- Lymphocytes exhibit varying receptor numbers depending on activation state; RBCs and platelets lack detectable receptors.
- No correlation was found between TNF receptor levels/affinity and TNF's cytotoxic effect on myeloid cell lines.
- Significant cytotoxic effects were observed at TNF concentrations substantially lower than those required for half-maximal receptor occupancy.
Conclusions:
- Biologically significant effects of TNF can manifest at low levels of receptor occupancy.
- Resistance to TNF in certain myeloid leukemic cell lines is not attributable to a lack of TNF receptors.