Inhibition of natural killer cytotoxicity by extracellular ppp(A2′p5′) nA oligonucleotides
The effect of purified 2′ – 5′ linked polyadenylated oligomers on the human natural killer (NK) activity has been investigated. Permeabilization of NK cells to ppp(A2′p5′) 2A did not enhance their NK activity at any concentration tested. Furthermore, concentrations higher than 0.1 mM inhibited their...
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| Veröffentlicht in: | International journal of immunopharmacology 1988, Vol.10 (1), p.73-80 |
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| creator | Alarcón, Balbino Redondo, Juan M. Bugany, Harald Carrasco, Luis Fresno, Manuel |
| description | The effect of purified 2′ – 5′ linked polyadenylated oligomers on the human natural killer (NK) activity has been investigated. Permeabilization of NK cells to ppp(A2′p5′)
2A did not enhance their NK activity at any concentration tested. Furthermore, concentrations higher than 0.1 mM inhibited their NK activity. Similar results were obtained by pre-incubating non-permeabilized intact cells, indicating an extracellular effect of these compounds on cell membranes, which was further investigated. This inhibition by the oligomers was greater (50% inhibition was obtained with 50 μm), when they were added directly to the NK assay, than when the NK cells were pre-incubated. Similar inhibitory effects were observed with ppp(A2′p5′)A and ppp(A2′p5′)
3A oligomers but not with the dephosphorylated “core” molecules or other nucleotides. The inhibition was completely or partially reversed by phorbol esters and by interferon (IFN) respectively. The inhibition was temperature and extracellular Ca
2+ dependent. The oligomers did not inhibit the binding of the effector cells to the target cells. The programming for lysis was the step of the lytic mechanism affected, possibly due to the alteration of the Ca
2+ influx into the NK cells observed in presence of the ppp(A2′p5′)
n
A. |
| doi_str_mv | 10.1016/0192-0561(88)90153-1 |
| format | Article |
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2A did not enhance their NK activity at any concentration tested. Furthermore, concentrations higher than 0.1 mM inhibited their NK activity. Similar results were obtained by pre-incubating non-permeabilized intact cells, indicating an extracellular effect of these compounds on cell membranes, which was further investigated. This inhibition by the oligomers was greater (50% inhibition was obtained with 50 μm), when they were added directly to the NK assay, than when the NK cells were pre-incubated. Similar inhibitory effects were observed with ppp(A2′p5′)A and ppp(A2′p5′)
3A oligomers but not with the dephosphorylated “core” molecules or other nucleotides. The inhibition was completely or partially reversed by phorbol esters and by interferon (IFN) respectively. The inhibition was temperature and extracellular Ca
2+ dependent. The oligomers did not inhibit the binding of the effector cells to the target cells. The programming for lysis was the step of the lytic mechanism affected, possibly due to the alteration of the Ca
2+ influx into the NK cells observed in presence of the ppp(A2′p5′)
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2A did not enhance their NK activity at any concentration tested. Furthermore, concentrations higher than 0.1 mM inhibited their NK activity. Similar results were obtained by pre-incubating non-permeabilized intact cells, indicating an extracellular effect of these compounds on cell membranes, which was further investigated. This inhibition by the oligomers was greater (50% inhibition was obtained with 50 μm), when they were added directly to the NK assay, than when the NK cells were pre-incubated. Similar inhibitory effects were observed with ppp(A2′p5′)A and ppp(A2′p5′)
3A oligomers but not with the dephosphorylated “core” molecules or other nucleotides. The inhibition was completely or partially reversed by phorbol esters and by interferon (IFN) respectively. The inhibition was temperature and extracellular Ca
2+ dependent. The oligomers did not inhibit the binding of the effector cells to the target cells. The programming for lysis was the step of the lytic mechanism affected, possibly due to the alteration of the Ca
2+ influx into the NK cells observed in presence of the ppp(A2′p5′)
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A.</description><subject>Adenine Nucleotides - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Calcium Chloride - pharmacokinetics</subject><subject>Cytotoxic reactions (adcc reaction, cell-mediated lympholysis, complement-dependent cytotoxicity and others)</subject><subject>Cytotoxicity, Immunologic</subject><subject>Dose-Response Relationship, Immunologic</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Humans</subject><subject>Immunobiology</subject><subject>Immunological reactions in vitro</subject><subject>In Vitro Techniques</subject><subject>Killer Cells, Natural - drug effects</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Oligoribonucleotides - pharmacology</subject><subject>Protein Synthesis Inhibitors - immunology</subject><subject>Protein Synthesis Inhibitors - pharmacology</subject><issn>0192-0561</issn><issn>1879-3495</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1u1DAQxy0EKtvCG4DkA0LtIa0dfyUXpFXVL6lSL-WKZTsTMPXGqe2g7q3PxCPxJM12V3vkMnOY34zm_0PoEyWnlFB5RmhbV0RIetw0Jy2hglX0DVrQRrUV4614ixZ75D06zPk3IURQWR-gA8akFJQt0I-b4Ze3vvg44NjjwZQpmYAffAiQsFuXWOKTd76ssV1jeCrJOAhhCibhcRyPl_W_57-jmMsJHpY4Bv8zDpMLEIvvIH9A73oTMnzc9SP0_fLi_vy6ur27ujlf3laOEVqqRlGwrmYguDXQt50EIgTt21pZy6lw4OQcuTdCccuVEsoSS7iwzsieGWBH6Ov27pji4wS56JXPm0fNAHHKWjU14ZLXM8i3oEsx5wS9HpNfmbTWlOiNVr1xpjfOdNPoV62azmufd_cnu4Juv7TzOM-_7OYmOxP6ZAbn8x5Tag4h5Ix922Iwu_jjIensPAwOOp_AFd1F__8_XgAaPJZm</recordid><startdate>1988</startdate><enddate>1988</enddate><creator>Alarcón, Balbino</creator><creator>Redondo, Juan M.</creator><creator>Bugany, Harald</creator><creator>Carrasco, Luis</creator><creator>Fresno, Manuel</creator><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>1988</creationdate><title>Inhibition of natural killer cytotoxicity by extracellular ppp(A2′p5′) nA oligonucleotides</title><author>Alarcón, Balbino ; Redondo, Juan M. ; Bugany, Harald ; Carrasco, Luis ; Fresno, Manuel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c301t-871ebc23e54baef9d6e0551f927bb415cec6016fa574b47757b0b045bca6f3ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>Adenine Nucleotides - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Calcium Chloride - pharmacokinetics</topic><topic>Cytotoxic reactions (adcc reaction, cell-mediated lympholysis, complement-dependent cytotoxicity and others)</topic><topic>Cytotoxicity, Immunologic</topic><topic>Dose-Response Relationship, Immunologic</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Humans</topic><topic>Immunobiology</topic><topic>Immunological reactions in vitro</topic><topic>In Vitro Techniques</topic><topic>Killer Cells, Natural - drug effects</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Oligoribonucleotides - pharmacology</topic><topic>Protein Synthesis Inhibitors - immunology</topic><topic>Protein Synthesis Inhibitors - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alarcón, Balbino</creatorcontrib><creatorcontrib>Redondo, Juan M.</creatorcontrib><creatorcontrib>Bugany, Harald</creatorcontrib><creatorcontrib>Carrasco, Luis</creatorcontrib><creatorcontrib>Fresno, Manuel</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alarcón, Balbino</au><au>Redondo, Juan M.</au><au>Bugany, Harald</au><au>Carrasco, Luis</au><au>Fresno, Manuel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of natural killer cytotoxicity by extracellular ppp(A2′p5′) nA oligonucleotides</atitle><jtitle>International journal of immunopharmacology</jtitle><addtitle>Int J Immunopharmacol</addtitle><date>1988</date><risdate>1988</risdate><volume>10</volume><issue>1</issue><spage>73</spage><epage>80</epage><pages>73-80</pages><issn>0192-0561</issn><eissn>1879-3495</eissn><coden>IJIMDS</coden><abstract>The effect of purified 2′ – 5′ linked polyadenylated oligomers on the human natural killer (NK) activity has been investigated. Permeabilization of NK cells to ppp(A2′p5′)
2A did not enhance their NK activity at any concentration tested. Furthermore, concentrations higher than 0.1 mM inhibited their NK activity. Similar results were obtained by pre-incubating non-permeabilized intact cells, indicating an extracellular effect of these compounds on cell membranes, which was further investigated. This inhibition by the oligomers was greater (50% inhibition was obtained with 50 μm), when they were added directly to the NK assay, than when the NK cells were pre-incubated. Similar inhibitory effects were observed with ppp(A2′p5′)A and ppp(A2′p5′)
3A oligomers but not with the dephosphorylated “core” molecules or other nucleotides. The inhibition was completely or partially reversed by phorbol esters and by interferon (IFN) respectively. The inhibition was temperature and extracellular Ca
2+ dependent. The oligomers did not inhibit the binding of the effector cells to the target cells. The programming for lysis was the step of the lytic mechanism affected, possibly due to the alteration of the Ca
2+ influx into the NK cells observed in presence of the ppp(A2′p5′)
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| fulltext | fulltext |
| identifier | ISSN: 0192-0561 |
| ispartof | International journal of immunopharmacology, 1988, Vol.10 (1), p.73-80 |
| issn | 0192-0561 1879-3495 |
| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adenine Nucleotides - pharmacology Biological and medical sciences Calcium Chloride - pharmacokinetics Cytotoxic reactions (adcc reaction, cell-mediated lympholysis, complement-dependent cytotoxicity and others) Cytotoxicity, Immunologic Dose-Response Relationship, Immunologic Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Immunobiology Immunological reactions in vitro In Vitro Techniques Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Oligoribonucleotides - pharmacology Protein Synthesis Inhibitors - immunology Protein Synthesis Inhibitors - pharmacology |
| title | Inhibition of natural killer cytotoxicity by extracellular ppp(A2′p5′) nA oligonucleotides |
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