Document Detail

Cell density-dependent regulation of cell surface expression of two types of human tumor necrosis factor receptors and its effect on cellular response.
MedLine Citation:
PMID:  8014194     Owner:  NLM     Status:  MEDLINE    
Tumor necrosis factor (TNF) is a multipotential cytokine known to regulate the growth of a wide variety of normal and tumor cells. It has been shown that the density of cells in culture can modulate the growth regulatory activities of TNF, the mechanism of which, however, is not understood. In this report, we investigated the effect of cell density on the expression of TNF receptors. The receptors were examined on epithelial cells (e.g., HeLa), which primarily express the p60 form, and on myeloid cells (e.g., HL-60) known to express mainly the p80 form. We observed that binding of TNF to both cell lines decreased with increase in cell density. Scatchard analysis of binding on HeLa and HL-60 cells revealed a 4- to 5-fold reduction in the number of TNF receptors without any significant change in receptor affinity in both cell types at high density. The decrease in TNF receptor numbers at high cell density was also observed in several other epithelial and myeloid cell lines. The downmodulation at high cell density was unique to TNF receptors, since minimum change in other cell surface proteins was observed as revealed by fluorescent activated cell sorter analysis. Neutralization of binding with antibodies specific to each type of the receptors revealed that both the p60 and p80 forms of the TNF receptor were equally downmodulated. A decrease in leucine incorporation into proteins was observed with increase in cell density, suggesting a reduction in protein synthesis. Since inhibition of protein synthesis by cycloheximide also leads to a decrease in TNF receptors, it is possible that the density-dependent reduction in TNF receptor number is due to an overall decrease in protein synthesis. The density-dependent decrease in TNF receptors was accompanied by a decrease in intracellular reduced glutathione levels. A reduction in the number of receptors on TNF sensitive tumor cells induced by cell-density correlated with increase in resistance to the cytokine.
E Pocsik; R Mihalik; F Ali-Osman; B B Aggarwal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  54     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-07-26     Completed Date:  1994-07-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  453-64     Citation Subset:  IM    
Department of Clinical Immunology and Biological Therapy, University of Texas M. D. Anderson Cancer Center, Houston 77030.
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MeSH Terms
Cell Count
Cell Division
Cell Membrane / metabolism*
Epithelium / metabolism
Glutathione / metabolism
Granulocytes / metabolism
Hela Cells / metabolism
Leukemia, Promyelocytic, Acute / metabolism
Protein Biosynthesis
Receptors, Tumor Necrosis Factor / metabolism*
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / metabolism
Reg. No./Substance:
0/Receptors, Tumor Necrosis Factor; 0/Tumor Necrosis Factor-alpha; 70-18-8/Glutathione

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