Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple Myeloma

The role of different receptors in natural-killer- (NK-) cell-mediated cytotoxicity against multiple myeloma (MM) cells is unknown. We investigated if an enhancement of NK-cell-mediated cytotoxicity against MM could be reached by blocking of the inhibitory leukocyte immunoglobulin-like receptor 1 (L...

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Main Authors: Silke Heidenreich, Christine zu Eulenburg, York Hildebrandt, Thomas Stübig, Heidi Sierich, Anita Badbaran, Thomas H. Eiermann, Thomas M. C. Binder, Nicolaus Kröger
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/652130
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author Silke Heidenreich
Christine zu Eulenburg
York Hildebrandt
Thomas Stübig
Heidi Sierich
Anita Badbaran
Thomas H. Eiermann
Thomas M. C. Binder
Nicolaus Kröger
author_facet Silke Heidenreich
Christine zu Eulenburg
York Hildebrandt
Thomas Stübig
Heidi Sierich
Anita Badbaran
Thomas H. Eiermann
Thomas M. C. Binder
Nicolaus Kröger
author_sort Silke Heidenreich
collection DOAJ
description The role of different receptors in natural-killer- (NK-) cell-mediated cytotoxicity against multiple myeloma (MM) cells is unknown. We investigated if an enhancement of NK-cell-mediated cytotoxicity against MM could be reached by blocking of the inhibitory leukocyte immunoglobulin-like receptor 1 (LIR-1). Our investigations revealed high levels of LIR-1 expression not only on the NK cell line NK-92, but also on myeloma cells (MOLP-8, RPMI8226) as well as on a lymphoblastoid cell line (LBCL; IM-9). Subsequent cytotoxicity assays were designed to show the isolated effects of LIR-1 blocking on either the effector or the tumor side to rule out receptor-receptor interactions. Although NK-92 was shown to be capable of myeloma cell lysis, inhibition of LIR-1 on NK-92 did not enhance cytotoxicity. Targeting the receptor on MM and LBCL did not also alter NK-92-mediated lysis. We come to the conclusion that LIR-1 alone does not directly influence NK-cell-mediated cytotoxicity against myeloma. To our knowledge, this work provides the first investigation of the inhibitory capability of LIR-1 in NK-92-mediated cytotoxicity against MM and the first functional evaluation of LIR-1 on MM and LBCL.
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spelling doaj-art-cf4a52680c1e4abfaecacfaadee406d52025-08-20T03:23:42ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/652130652130Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple MyelomaSilke Heidenreich0Christine zu Eulenburg1York Hildebrandt2Thomas Stübig3Heidi Sierich4Anita Badbaran5Thomas H. Eiermann6Thomas M. C. Binder7Nicolaus Kröger8Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyClinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyClinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyClinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyClinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyThe role of different receptors in natural-killer- (NK-) cell-mediated cytotoxicity against multiple myeloma (MM) cells is unknown. We investigated if an enhancement of NK-cell-mediated cytotoxicity against MM could be reached by blocking of the inhibitory leukocyte immunoglobulin-like receptor 1 (LIR-1). Our investigations revealed high levels of LIR-1 expression not only on the NK cell line NK-92, but also on myeloma cells (MOLP-8, RPMI8226) as well as on a lymphoblastoid cell line (LBCL; IM-9). Subsequent cytotoxicity assays were designed to show the isolated effects of LIR-1 blocking on either the effector or the tumor side to rule out receptor-receptor interactions. Although NK-92 was shown to be capable of myeloma cell lysis, inhibition of LIR-1 on NK-92 did not enhance cytotoxicity. Targeting the receptor on MM and LBCL did not also alter NK-92-mediated lysis. We come to the conclusion that LIR-1 alone does not directly influence NK-cell-mediated cytotoxicity against myeloma. To our knowledge, this work provides the first investigation of the inhibitory capability of LIR-1 in NK-92-mediated cytotoxicity against MM and the first functional evaluation of LIR-1 on MM and LBCL.http://dx.doi.org/10.1155/2012/652130
spellingShingle Silke Heidenreich
Christine zu Eulenburg
York Hildebrandt
Thomas Stübig
Heidi Sierich
Anita Badbaran
Thomas H. Eiermann
Thomas M. C. Binder
Nicolaus Kröger
Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple Myeloma
Clinical and Developmental Immunology
title Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple Myeloma
title_full Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple Myeloma
title_fullStr Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple Myeloma
title_full_unstemmed Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple Myeloma
title_short Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple Myeloma
title_sort impact of the nk cell receptor lir 1 ilt 2 cd85j lilrb1 on cytotoxicity against multiple myeloma
url http://dx.doi.org/10.1155/2012/652130
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