Abstract
TNF-α can induce cell death (apoptosis and necrosis), and these effects mostly depend on expression of TNF-receptor superfamily molecules. As determination of certain intracellular enzymes like LDH, released from cultured tumor cells, reflects early membrane alterations, we compared LDH release with changes in cell surface membrane molecule expression during culture of K-562 cells in the presence of TNF-α. TNF-α-mediated CD45 and CD30 shedding is shown to be to be time- and dose-dependent and associated with significant increase in LDH release, with maximal effects after 24 h of treatment. The percentage of decrease of all examined cell surface molecules on K-562 cells after TNF-α treatment was not uniform and appeared to depend on the respective constitutive level of expression and molecule type. The presence of these molecules was confirmed in supernatants using Western blot analyses. These results indicated the complexity of events on the cell membrane, including early LDH release that is associated with a difference in shedding of CD30 and CD45. Shedding of CD30 occurs before apoptosis induction, while shedding of CD45 is associated with apoptosis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andreakos ET, Foxwell BM, Brennan FM, Maini RN, Feldman M (2002) Cytokines and anti-cytokine biologicals in autoimmunity present and future. Citokine Growth Factor Rev 13:299–313
Arnott HC, Scott KA, Moore RJ, Hewer A, Philips HD, Parker P, Balkwill FR, Owens DM (2002) Tumor necrosis factor-α mediates tumor promotion via a PKCα-and AP-1-dependent pathway. Oncogene 21:4728–4738
Barbui AM, Borleri G, Conti E, Ciocca A, Salvi A, Mico C, Introona M, Rambaldi A (2006) Clinical grade expansion of CD45 RA, CD45RO, and CD62L-positive T-cell lines from HLA-compatible donors: high cytotoxic potential agains AML and ALL cells. Exp Hematol 34:474–485
Chen W, Wang HG, Srinivasula SM, Alnemri ES, Cooper NR (1999) B cell apoptosis triggered by antigen receptor ligation proceeds via a novel caspase-dependent pathway. J Immunol 163:2489–2491
Decker T, Lohmann-Matther ML (1998) A quick and simple method for quantitation of lactate dehydrogenase release in measurement of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 15:61–67
Eichenauer DA, Simhadri VL, von Strandmann P, Ludwig A, Matthews V, Reiners KS, von Tresckow B, Safting P, Rose-John S, Engert A, Hansen HP (2007) ADAM 10 inhibition of human CD30 shedding increases specificity of target immunotherapy in vitro. Cancer Res 7:332–338
Goto N, Maeyama J, Yasuda Y (2000) Safety evaluation of recombinant cholera toxin B subunit producer by Bacillus brevis as a mucosal adjuvant. Vaccine 18:2164–2171
Grell M, Zimmermann G, Hulser D, Pfizenmaier K, Scheurich P (1994) TNF receptors TR60 and TR80 can mediate apoptosis via induction of distinct signal pathways. J Immunol 153:1963–1972
Haggins CF (1999) Membrane permeability transporters and channels: from disease to structure and back. Curr Opin Cell Biol 11:495–499
Haranaka K, Satomi N (1991) Cytotoxic activity of tumor necrosis factor (TNF) on human cancer cells in vitro. Jpn J Exp Med 51:191–194
Hu X (2003) Proteolytic signaling by TNFα: caspase activation and IkB degradation. Cytokine 21:286–294
Jupp OJ, Vandenabeele P, MacEwan DJ (2003) Distinct regulation of cytosolic phospholipase A2 phosphorylation, translocation, proteolysis and activation by tumor necrosis factor-receptor subtype. Biochem J 374:453–461
Jurisic V (2003) Estimation of cell membrane alteration after drug treatment by LDH release. Blood 101:2894
Jurisic V, Konjevic G, Spuzic I (1999) A comparison of NK cell cytotoxicity with effects of TNF-alfa against K-562 cells, determined by LDH release assay. Cancer Lett 138:670–672
Jurisic V, Konjevic G, Banicevic B, Djuricic B, Spuzic I (2000) Different alterations in lactate dehydrogenase activity and profile of peripheral blood mononuclear cells in Hodgkin’s and non-Hodgkin’s lymphomas. Eur J Haematol 64:259–266
Konjevic G, Jurisic V, Spuzic I (1997) Corrections to the original lactate dehydrogenase (LDH) release assay for the evaluation of NK cell cytotoxicity. J Immunol Meth 200:199–201.
Konjevic G, Jurisic V, Spuzic I (2001) Association of NK cell dysfunction with changes in LDH characteristics of peripheral blood lymphocytes (PBL) in breast cancer patients. Breast Cancer Res Treat 66:255–263
Kumamura S, Ishikura H, Tsumura H, Iwata Y, Endo J, Kobayashi S (1996) c-Myc and Bcl-2 protein expression during the induction of apoptosis and differentiation in TNF-α treated HL-60 cells. Leuk Lymphoma 23:383–394
MacEwan DJ (2002) TNF ligands and receptors—a matter of life and death. Br J Pharmacol 135:855–875
Marjanovic S, Skog S, Heiden T, Tribukait B, Nelson BD (1991) Expression of glycolytic enzymes in activated human peripheral lymphocytes: cell cycle analysis using flow cytometry. Exp Cell Res 193:425–431
Meilhac O, Escargueil-Blanc I, Thiers JC, Salvayre R, Salvayre-Negre A (1999) Bcl-2 alters the balance between apoptosis and necrosis, but does not prevent cell death induced by oxidized low density lipoproteins. FASEB J 13:485–494
Nehar D, Mausuit C, Boussouar F, Benahmed M (1997) Tumor necrosis factor alpha stimulated lactate production is linked to lactate dehydrogenase A expression and activity increase in porcine cultured Sertoli cells. Endocrinology 138:1964–1971
Okazaki T, Kondo T, Kitano T, Tashima M (1998) Diversity and complexity of ceramide signalling in apoptosis. Cell Signal 10:685–692
Penninger JM, Sasaki JI, Sasaki T, Olivera-dos-Santos AJ (2001) CD45: new jobs for an old acquaintance. Nat Immunol 2:389–396
Pollock PV, Lofthouse EJ, Jupp JO, Stephen BC, Gauld BS, Anderson MH, MacEwan JD (2000) Selective down-regulation of the Gqa/G11a G protein family in tumor necrosis factor-α induced cell death. Mol Cell Biochem 206:67–74
Porter AG (1999) Protein transport in apoptosis. Trends Cell Biol 9:394–401
Smith CA, Farrah T, Goodwin G (1994) The TNF receptor superfamily of cellular and viral proteins: activation, costimulation and death. Cell 76:959–962
Tibbles LA, Woodgett JR (1999) The stress-activted protein kinase pathways. Cell Mol Life Sci 55:1230–1254
Vahdat AM, Reiners KS, Simhadri VL, Eichenauer DA, Boll B, Chalaris A, Simhadri VR, Wiegmann K, Krell HW, Rose-John S, Engert A, von Strandmann EP, Hansen HP (2010) TNF-α-converting enzyme (TACE/ADAM17)-dependent loss of CD30 induced by proteasome inhibition through reactive oxygen species. Leukemia 24:51–57
Vajant H, Scheurich P (2001) Tumor necrosis factor receptor-associated factor (TRAF2) and its role in TNF signaling. Int J Biochem Cell Biol 33:19–32
Voelkel-Jonson C, Entingh AJ, Wold SMW (1995) Activation of intracellular proteases is an early event in TNF-induced apoptosis. Immunology 154:1707–1716
Weidmann E, Brieger J, Jahn B, Hoelzer D, Bergmann L, Mitrou PS (1995) Lactate dehydrogenase-release assay: a reliable, non-radioactive technique for analysis of cytotoxic lymphocyte-mediated lytic activity against blast from acute myelocytic leukemia. Ann Hematol 70:153–158
Wissing D, Mouritzen H, Egeblad M, Poirier GG, Jaattela M (1997) Involvement of caspase-dependent activation of cytosolic phospholipase A2 in tumor necrosis factor-induced apoptosis. Proc Natl Acad Sci USA 94:5073–5077
Acknowledgments
This work was supported by the Ministry of Science and Technology of the Republic of Serbia.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jurisic, V., Srdic-Rajic, T., Konjevic, G. et al. TNF-α Induced Apoptosis is Accompanied with Rapid CD30 and Slower CD45 Shedding from K-562 Cells. J Membrane Biol 239, 115–122 (2011). https://doi.org/10.1007/s00232-010-9309-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00232-010-9309-7