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Cell density-dependent regulation of cell surface expression of two types of human tumor necrosis factor receptors and its effect on cellular response.

Publication ,  Journal Article
Pocsik, E; Mihalik, R; Ali-Osman, F; Aggarwal, BB
Published in: J Cell Biochem
April 1994

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.

Duke Scholars

Published In

J Cell Biochem

DOI

ISSN

0730-2312

Publication Date

April 1994

Volume

54

Issue

4

Start / End Page

453 / 464

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Receptors, Tumor Necrosis Factor
  • Protein Biosynthesis
  • Leukemia, Promyelocytic, Acute
  • Humans
  • Hela Cells
  • HeLa Cells
  • Granulocytes
  • Glutathione
 

Citation

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Pocsik, E., Mihalik, R., Ali-Osman, F., & Aggarwal, B. B. (1994). Cell density-dependent regulation of cell surface expression of two types of human tumor necrosis factor receptors and its effect on cellular response. J Cell Biochem, 54(4), 453–464. https://doi.org/10.1002/jcb.240540412
Pocsik, E., R. Mihalik, F. Ali-Osman, and B. B. Aggarwal. “Cell density-dependent regulation of cell surface expression of two types of human tumor necrosis factor receptors and its effect on cellular response.J Cell Biochem 54, no. 4 (April 1994): 453–64. https://doi.org/10.1002/jcb.240540412.
Pocsik, E., et al. “Cell density-dependent regulation of cell surface expression of two types of human tumor necrosis factor receptors and its effect on cellular response.J Cell Biochem, vol. 54, no. 4, Apr. 1994, pp. 453–64. Pubmed, doi:10.1002/jcb.240540412.
Journal cover image

Published In

J Cell Biochem

DOI

ISSN

0730-2312

Publication Date

April 1994

Volume

54

Issue

4

Start / End Page

453 / 464

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Receptors, Tumor Necrosis Factor
  • Protein Biosynthesis
  • Leukemia, Promyelocytic, Acute
  • Humans
  • Hela Cells
  • HeLa Cells
  • Granulocytes
  • Glutathione