Allosteric LFA-1 Inhibitors Modulate Natural Killer Cell Function
Natural killer (NK) cells are believed to play an important role in a variety of disease pathologies, including transplant rejection and autoimmunity. None of the therapeutic modalities currently available are known to potently interfere with NK cell activity. Here we demonstrate for the first time...
Saved in:
Published in | Molecular pharmacology Vol. 75; no. 2; pp. 355 - 362 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.02.2009
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Natural killer (NK) cells are believed to play an important role in a variety of disease pathologies, including transplant
rejection and autoimmunity. None of the therapeutic modalities currently available are known to potently interfere with NK
cell activity. Here we demonstrate for the first time that low molecular weight inhibitors of the integrin lymphocyte function-associated
antigen-1 (LFA-1) readily block NK cell adhesion, activation, and NK cell-mediated cytolysis in vitro, in contrast to other
immunosuppressive agents. These effects were independent of the type of allosteric mechanism by which LFA-1 inhibition was
achieved. In addition, we describe a simple, nonradioactive whole-blood assay that should be suitable to monitor NK cell activation
in clinical practice. Taken together, our study underlines the importance of LFA-1 in NK cell effector functions and indicates
that allosteric LFA-1 inhibitors may become important tools to further elucidate the therapeutic potential of NK cell modulation
in immunological diseases. |
---|---|
AbstractList | Natural killer (NK) cells are believed to play an important role in a variety of disease pathologies, including transplant
rejection and autoimmunity. None of the therapeutic modalities currently available are known to potently interfere with NK
cell activity. Here we demonstrate for the first time that low molecular weight inhibitors of the integrin lymphocyte function-associated
antigen-1 (LFA-1) readily block NK cell adhesion, activation, and NK cell-mediated cytolysis in vitro, in contrast to other
immunosuppressive agents. These effects were independent of the type of allosteric mechanism by which LFA-1 inhibition was
achieved. In addition, we describe a simple, nonradioactive whole-blood assay that should be suitable to monitor NK cell activation
in clinical practice. Taken together, our study underlines the importance of LFA-1 in NK cell effector functions and indicates
that allosteric LFA-1 inhibitors may become important tools to further elucidate the therapeutic potential of NK cell modulation
in immunological diseases. Natural killer (NK) cells are believed to play an important role in a variety of disease pathologies, including transplant rejection and autoimmunity. None of the therapeutic modalities currently available are known to potently interfere with NK cell activity. Here we demonstrate for the first time that low molecular weight inhibitors of the integrin lymphocyte function-associated antigen-1 (LFA-1) readily block NK cell adhesion, activation, and NK cell-mediated cytolysis in vitro, in contrast to other immunosuppressive agents. These effects were independent of the type of allosteric mechanism by which LFA-1 inhibition was achieved. In addition, we describe a simple, nonradioactive whole-blood assay that should be suitable to monitor NK cell activation in clinical practice. Taken together, our study underlines the importance of LFA-1 in NK cell effector functions and indicates that allosteric LFA-1 inhibitors may become important tools to further elucidate the therapeutic potential of NK cell modulation in immunological diseases. |
Author | Gabriele Weitz-Schmidt Simone Riek Stéphanie Chreng |
Author_xml | – sequence: 1 fullname: Gabriele Weitz-Schmidt – sequence: 2 fullname: Stéphanie Chreng – sequence: 3 fullname: Simone Riek |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18955586$$D View this record in MEDLINE/PubMed |
BookMark | eNpFkE1LAzEQhoNU7IdePcpe9LY1k2yy2WMpVotVLwreQpqkbSS7qcku0n_vSgueZhie92V4xmjQhMYidA14CkCK-zr4KWAxxQyAV2doBIxAjgFggEYYE56Lin0O0TilL4yhYAJfoCH0R8YEH6HZzPuQWhudzlaLWQ7Zstm5tWtDTNlLMJ1Xrc1eVdtF5bNn572N2dx6ny26RrcuNJfofKN8slenOUEfi4f3-VO-entczmerXFNC23zNORHUCFWVlcUlN8SWGoBVxrAKYK1LgIKD3hQV0aAM5cSU2myoLoSm2NIJujv27mP47mxqZe2S7j9RjQ1dkpyLArigPTg9gjqGlKLdyH10tYoHCVj-SZO9tH4X8iitD9ycmrt1bc0_frLUA7dHYOe2ux8XrdzvVKyVDj5sD7JkkkjKGP0FboR1iQ |
CitedBy_id | crossref_primary_10_1002_ange_201310240 crossref_primary_10_1002_anie_201310240 crossref_primary_10_1038_bmt_2011_22 crossref_primary_10_1155_2021_2563093 crossref_primary_10_4049_jimmunol_1002438 crossref_primary_10_1128_AAC_00117_09 crossref_primary_10_1016_j_imlet_2016_11_015 crossref_primary_10_3390_ijms222413495 crossref_primary_10_1089_aid_2011_0395 crossref_primary_10_1016_j_toxlet_2016_12_007 |
Cites_doi | 10.4049/jimmunol.179.3.1616 10.1016/S0065-2776(04)86006-1 10.1006/jmbi.1999.3047 10.1084/jem.183.4.1415 10.1038/89058 10.1074/jbc.M110521200 10.1111/j.1600-065X.2006.00457.x 10.1093/intimm/dxl133 10.1111/j.1365-2133.2008.08548.x 10.1089/152581601750288975 10.1016/j.it.2005.08.008 10.1016/S0041-1345(98)00587-9 10.1016/0022-1759(95)00116-R 10.1016/S1074-7613(03)00238-3 10.1097/01.TP.0000083896.91215.C7 10.1056/NEJMra033540 10.1038/ni1582 10.1016/S0002-9149(97)00695-4 10.4049/jimmunol.178.3.1261 10.1016/j.it.2007.03.005 10.1182/blood-2006-10-048173 10.1002/jcp.1041390314 10.1038/nm1008-1050 10.1016/j.transproceed.2008.04.006 10.2174/1568026043387575 10.1074/jbc.M407951200 10.1016/j.trim.2008.01.004 10.1097/00007890-198102000-00004 10.4049/jimmunol.173.6.3653 10.1078/0171-2985-00219 10.1182/blood-2003-08-2652 10.1097/01.tp.0000296817.28053.7b 10.1016/j.cellimm.2008.07.004 10.1046/j.1600-065X.2003.00090.x 10.1002/1097-0320(20001201)41:4<289::AID-CYTO7>3.0.CO;2-5 |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION 7X8 |
DOI | 10.1124/mol.108.051169 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef MEDLINE - Academic |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef MEDLINE - Academic |
DatabaseTitleList | MEDLINE - Academic MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Pharmacy, Therapeutics, & Pharmacology |
EISSN | 1521-0111 |
EndPage | 362 |
ExternalDocumentID | 10_1124_mol_108_051169 18955586 75_2_355 |
Genre | Journal Article |
GroupedDBID | - 0R 123 2WC 34G 39C 4.4 53G 55 5RE 5VS AALRV AAPBV ABFLS ABSGY ABZEH ACGFS ADACO ADBIT ADCOW AENEX AFFNX ALMA_UNASSIGNED_HOLDINGS CS3 DIK DL E3Z EBS EJD F5P FH7 GX1 H13 HH5 HZ IH2 INIJC KQ8 L7B N9A O0- O9- OK1 P2P R.V R0Z RHF RHI RPT WOQ X X7M ZA5 --- -~X .55 .GJ 0R~ 18M AAJMC ABCQX ABJNI ABSQV ACGFO ADBBV AERNN AFHIN AFOSN AYCSE BAWUL BTFSW CGR CUY CVF ECM EIF F9R HZ~ K-O LSO MVM NPM TR2 UQL W8F XOL YBU YHG ZGI ZXP AAYXX CITATION 7X8 |
ID | FETCH-LOGICAL-c323t-b66283d8a979e076d2e7c1159dd5911bc711461cf492c1ad362d7cdf3c48c30e3 |
ISSN | 0026-895X |
IngestDate | Sat Aug 17 00:24:46 EDT 2024 Fri Aug 23 00:48:35 EDT 2024 Sat Sep 28 07:48:05 EDT 2024 Tue Jan 05 21:17:31 EST 2021 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 2 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c323t-b66283d8a979e076d2e7c1159dd5911bc711461cf492c1ad362d7cdf3c48c30e3 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
PMID | 18955586 |
PQID | 66841683 |
PQPubID | 23479 |
PageCount | 8 |
ParticipantIDs | proquest_miscellaneous_66841683 crossref_primary_10_1124_mol_108_051169 pubmed_primary_18955586 highwire_pharmacology_75_2_355 |
ProviderPackageCode | RHF RHI |
PublicationCentury | 2000 |
PublicationDate | 20090201 2009-Feb 2009-02-00 |
PublicationDateYYYYMMDD | 2009-02-01 |
PublicationDate_xml | – month: 02 year: 2009 text: 20090201 day: 01 |
PublicationDecade | 2000 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Molecular pharmacology |
PublicationTitleAlternate | Mol Pharmacol |
PublicationYear | 2009 |
Publisher | American Society for Pharmacology and Experimental Therapeutics |
Publisher_xml | – name: American Society for Pharmacology and Experimental Therapeutics |
References | 2019081413551629000_75.2.355.9 (2019081413551629000_75.2.355.37) 2004; 78 (2019081413551629000_75.2.355.12) 1981; 31 2019081413551629000_75.2.355.20 2019081413551629000_75.2.355.21 2019081413551629000_75.2.355.22 2019081413551629000_75.2.355.23 2019081413551629000_75.2.355.24 2019081413551629000_75.2.355.25 2019081413551629000_75.2.355.26 2019081413551629000_75.2.355.27 2019081413551629000_75.2.355.28 2019081413551629000_75.2.355.18 2019081413551629000_75.2.355.19 (2019081413551629000_75.2.355.3) 1991; 23 2019081413551629000_75.2.355.30 2019081413551629000_75.2.355.31 2019081413551629000_75.2.355.10 2019081413551629000_75.2.355.32 2019081413551629000_75.2.355.11 2019081413551629000_75.2.355.33 2019081413551629000_75.2.355.34 2019081413551629000_75.2.355.13 2019081413551629000_75.2.355.35 2019081413551629000_75.2.355.14 2019081413551629000_75.2.355.36 2019081413551629000_75.2.355.15 2019081413551629000_75.2.355.16 2019081413551629000_75.2.355.17 2019081413551629000_75.2.355.29 2019081413551629000_75.2.355.1 2019081413551629000_75.2.355.2 2019081413551629000_75.2.355.4 2019081413551629000_75.2.355.5 2019081413551629000_75.2.355.6 2019081413551629000_75.2.355.7 2019081413551629000_75.2.355.8 |
References_xml | – ident: 2019081413551629000_75.2.355.9 doi: 10.4049/jimmunol.179.3.1616 – ident: 2019081413551629000_75.2.355.2 doi: 10.1016/S0065-2776(04)86006-1 – ident: 2019081413551629000_75.2.355.15 doi: 10.1006/jmbi.1999.3047 – volume: 78 start-page: 1 year: 2004 ident: 2019081413551629000_75.2.355.37 publication-title: Transplantation – ident: 2019081413551629000_75.2.355.25 doi: 10.1084/jem.183.4.1415 – ident: 2019081413551629000_75.2.355.34 doi: 10.1038/89058 – ident: 2019081413551629000_75.2.355.36 doi: 10.1074/jbc.M110521200 – ident: 2019081413551629000_75.2.355.4 doi: 10.1111/j.1600-065X.2006.00457.x – ident: 2019081413551629000_75.2.355.29 doi: 10.1093/intimm/dxl133 – ident: 2019081413551629000_75.2.355.16 doi: 10.1111/j.1365-2133.2008.08548.x – ident: 2019081413551629000_75.2.355.18 doi: 10.1089/152581601750288975 – ident: 2019081413551629000_75.2.355.14 doi: 10.1016/j.it.2005.08.008 – ident: 2019081413551629000_75.2.355.26 doi: 10.1016/S0041-1345(98)00587-9 – ident: 2019081413551629000_75.2.355.13 doi: 10.1016/0022-1759(95)00116-R – volume: 23 start-page: 1867 year: 1991 ident: 2019081413551629000_75.2.355.3 publication-title: Transplant Proc – ident: 2019081413551629000_75.2.355.27 doi: 10.1016/S1074-7613(03)00238-3 – ident: 2019081413551629000_75.2.355.30 doi: 10.1097/01.TP.0000083896.91215.C7 – ident: 2019081413551629000_75.2.355.10 doi: 10.1056/NEJMra033540 – ident: 2019081413551629000_75.2.355.31 doi: 10.1038/ni1582 – ident: 2019081413551629000_75.2.355.19 doi: 10.1016/S0002-9149(97)00695-4 – ident: 2019081413551629000_75.2.355.20 doi: 10.4049/jimmunol.178.3.1261 – ident: 2019081413551629000_75.2.355.11 doi: 10.1016/j.it.2007.03.005 – ident: 2019081413551629000_75.2.355.33 doi: 10.1182/blood-2006-10-048173 – ident: 2019081413551629000_75.2.355.6 doi: 10.1002/jcp.1041390314 – ident: 2019081413551629000_75.2.355.7 doi: 10.1038/nm1008-1050 – ident: 2019081413551629000_75.2.355.17 doi: 10.1016/j.transproceed.2008.04.006 – ident: 2019081413551629000_75.2.355.28 doi: 10.2174/1568026043387575 – ident: 2019081413551629000_75.2.355.35 doi: 10.1074/jbc.M407951200 – ident: 2019081413551629000_75.2.355.8 doi: 10.1016/j.trim.2008.01.004 – volume: 31 start-page: 113 year: 1981 ident: 2019081413551629000_75.2.355.12 publication-title: Transplantation doi: 10.1097/00007890-198102000-00004 – ident: 2019081413551629000_75.2.355.1 doi: 10.4049/jimmunol.173.6.3653 – ident: 2019081413551629000_75.2.355.5 doi: 10.1078/0171-2985-00219 – ident: 2019081413551629000_75.2.355.21 doi: 10.1182/blood-2003-08-2652 – ident: 2019081413551629000_75.2.355.32 doi: 10.1097/01.tp.0000296817.28053.7b – ident: 2019081413551629000_75.2.355.23 doi: 10.1016/j.cellimm.2008.07.004 – ident: 2019081413551629000_75.2.355.24 doi: 10.1046/j.1600-065X.2003.00090.x – ident: 2019081413551629000_75.2.355.22 doi: 10.1002/1097-0320(20001201)41:4<289::AID-CYTO7>3.0.CO;2-5 |
SSID | ssj0014580 |
Score | 2.0145488 |
Snippet | Natural killer (NK) cells are believed to play an important role in a variety of disease pathologies, including transplant
rejection and autoimmunity. None of... Natural killer (NK) cells are believed to play an important role in a variety of disease pathologies, including transplant rejection and autoimmunity. None of... |
SourceID | proquest crossref pubmed highwire |
SourceType | Aggregation Database Index Database Publisher |
StartPage | 355 |
SubjectTerms | Biophysical Phenomena Cell Adhesion - drug effects Cell Adhesion - physiology Humans K562 Cells Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Killer Cells, Natural - physiology Lymphocyte Function-Associated Antigen-1 - drug effects Lymphocyte Function-Associated Antigen-1 - metabolism Lymphocyte Function-Associated Antigen-1 - physiology Signal Transduction - physiology |
Title | Allosteric LFA-1 Inhibitors Modulate Natural Killer Cell Function |
URI | http://molpharm.aspetjournals.org/content/75/2/355.abstract https://www.ncbi.nlm.nih.gov/pubmed/18955586 https://search.proquest.com/docview/66841683 |
Volume | 75 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3Nb9MwFLdgXLggvimD4QMahyyjsZM4OVZopUJlTCyVerMcx9GitenUZYftr-f5q2kFiI9LVKWKq7zfr8_Pz36_h9D7LGdlAjNfqJQQIfwT8zCrhQqprADjWiYR1dXIX0_TySz-Mk_mvtG4qy7pymN598u6kv9BFe4BrrpK9h-Q3QwKN-Az4AtXQBiuf4XxaLHQNRr6MPx0PAqjoGkvmrIxDXSWq0p35lKBke4EIC5N1V-gM_WBns02iPh-Tr5RbnDVy1n3CXfVdHfhubxYNpXx259FudbF6f35gLVyqefO7r7DMG2z-f57o4zjPQdyuK18n2zI_flkPVc4B0l0-sE5SOdBbe8TxxSy5Q6pleB1Myu1fvdnp01isPRytdAHHo_BS0S2e8uuOvbpNz6eTae8OJkX99EDwvLEqPpONsudKE6yoRPmhDE_7o64G3h4MejfLyxMgFE8Ro_cygCPLMxP0D3VPkWHZxaL2yNc9JVy10f4EJ9tofQMjXouYMMF3HMBey5gxwVsuYA1F7DnwnM0G58Unyaha48RSkpoF5ZpCrFhlYmc5WrI0oooJiHAz6sqgSmslExXnEeyjnMiI1GB-Ssmq5rKOJN0qOgLtNcC4q8QToZCMB381_CIkLIkMVVSaPE_mbFSDtAHbzt-ZVVQuFk9kpiDlbXKLLdWHqADb1q-zVbOEk448GGA3nmDc_Bk-kVFq1Y31zxN9RZ4RgfopcWh_6ks17J06es_PruPHva0fYP2uvWNegtRY1ceGKr8AI1ycLM |
link.rule.ids | 315,786,790,27955,27956 |
linkProvider | ABC ChemistRy |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Allosteric+LFA-1+inhibitors+modulate+natural+killer+cell+function&rft.jtitle=Molecular+pharmacology&rft.au=Weitz-Schmidt%2C+Gabriele&rft.au=Chreng%2C+St%C3%A9phanie&rft.au=Riek%2C+Simone&rft.date=2009-02-01&rft.eissn=1521-0111&rft.volume=75&rft.issue=2&rft.spage=355&rft.epage=362&rft_id=info:doi/10.1124%2Fmol.108.051169&rft.externalDBID=NO_FULL_TEXT |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0026-895X&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0026-895X&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0026-895X&client=summon |