Role of Nonspecific Cytotoxic Cells in the Induction of Programmed Cell Death of Pathogenic Protozoans: Participation of the Fas Ligand-Fas Receptor System

Jaso-Friedmann, L., Leary, J. H. III, and Evans D. L. 2000. Role of nonspecific cytotoxic cells in the induction of programmed cell death of pathogenic protozoans: Participation of the Fas ligand-Fas receptor system. Experimental Parasitology96, 75–88. Numerous different species of parasites and pat...

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Veröffentlicht in:Experimental parasitology 2000-10, Vol.96 (2), p.75-88
Hauptverfasser: Jaso-Friedmann, Liliana, Leary, John H., Evans, Donald L.
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description Jaso-Friedmann, L., Leary, J. H. III, and Evans D. L. 2000. Role of nonspecific cytotoxic cells in the induction of programmed cell death of pathogenic protozoans: Participation of the Fas ligand-Fas receptor system. Experimental Parasitology96, 75–88. Numerous different species of parasites and pathogenic microorganisms produce programmed cell death (PCD) and apoptosis in eukaryotic targets. How ever, only a few studies have demonstrated that effector cells, cytokines, growth factors, or soluble apoptosis-inducing factors are capable of initiating apoptosis in protozoan parasites. Certain Tetrahymena spp. in teleosts are opportunistic pathogens. In the present study these pathogenic protozoans were developed as a model system to describe the potential role of the Fas ligand (FasL)-Fas receptor (FasR) system as a means of innate immunity in teleosts. Nonspecific cytotoxic cells (NCC) constitutively express soluble FasL (sFasL). Binding of the antigen receptor (i.e., NCCRP-1) on NCC to target cells caused the release of sFasL into the milieu. The presence of functional sFasL in these supernatants was determined by Western blot analysis and by demonstrating the lysis of FasR+ HL-60 but not IM-9 (FasR−) targets. Soluble FasL containing supernatants generated by tumor cell-activated NCC also produced a reduction in 2 N DNA (i.e., DNA hypoploidy) of T. furgasoni. The induction of DNA hypoploidy by NCC supernatants could be neutralized by adsorption of the supernatants with anti-FasL antibody (but not with an isotype control). Experiments were next done to determine the expression of FasR on Tetrahymena and study the effects of anti-FasR monoclonal crosslinkage and treatment with soluble human recombinant FasL (huFasL) on initiation of PCD in Tetrahymena. Cell cycle analysis revealed that both crosslinkage and soluble huFasL binding to Tetrahymena produced DNA hypoploidy. The reduction in diploid DNA was confirmed by observing oligonucleosome fragmentation (DNA laddering) following anti-FasR treatment. Additional evidence for FasR expression on Tetrahymena was obtained using fluorescence microscopy and flow cytometry. Both methods showed that all Tetrahymena examined (three species consisting of four isolates) expressed membrane FasR. These studies demonstrated the potential of the FasL-FasR system in teleosts for initiation of antiparasite innate immunity. Effector NCC may initiate PCD of Tetrahymena that express a FasR-like protein. Induction of apoptosis may
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H. III, and Evans D. L. 2000. Role of nonspecific cytotoxic cells in the induction of programmed cell death of pathogenic protozoans: Participation of the Fas ligand-Fas receptor system. Experimental Parasitology96, 75–88. Numerous different species of parasites and pathogenic microorganisms produce programmed cell death (PCD) and apoptosis in eukaryotic targets. How ever, only a few studies have demonstrated that effector cells, cytokines, growth factors, or soluble apoptosis-inducing factors are capable of initiating apoptosis in protozoan parasites. Certain Tetrahymena spp. in teleosts are opportunistic pathogens. In the present study these pathogenic protozoans were developed as a model system to describe the potential role of the Fas ligand (FasL)-Fas receptor (FasR) system as a means of innate immunity in teleosts. Nonspecific cytotoxic cells (NCC) constitutively express soluble FasL (sFasL). Binding of the antigen receptor (i.e., NCCRP-1) on NCC to target cells caused the release of sFasL into the milieu. The presence of functional sFasL in these supernatants was determined by Western blot analysis and by demonstrating the lysis of FasR+ HL-60 but not IM-9 (FasR−) targets. Soluble FasL containing supernatants generated by tumor cell-activated NCC also produced a reduction in 2 N DNA (i.e., DNA hypoploidy) of T. furgasoni. The induction of DNA hypoploidy by NCC supernatants could be neutralized by adsorption of the supernatants with anti-FasL antibody (but not with an isotype control). Experiments were next done to determine the expression of FasR on Tetrahymena and study the effects of anti-FasR monoclonal crosslinkage and treatment with soluble human recombinant FasL (huFasL) on initiation of PCD in Tetrahymena. Cell cycle analysis revealed that both crosslinkage and soluble huFasL binding to Tetrahymena produced DNA hypoploidy. The reduction in diploid DNA was confirmed by observing oligonucleosome fragmentation (DNA laddering) following anti-FasR treatment. Additional evidence for FasR expression on Tetrahymena was obtained using fluorescence microscopy and flow cytometry. Both methods showed that all Tetrahymena examined (three species consisting of four isolates) expressed membrane FasR. These studies demonstrated the potential of the FasL-FasR system in teleosts for initiation of antiparasite innate immunity. Effector NCC may initiate PCD of Tetrahymena that express a FasR-like protein. Induction of apoptosis may be a major mechanism of homeostatic control of protozoan parasite infestations/infections.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1006/expr.2000.4561</identifier><identifier>PMID: 11052866</identifier><identifier>CODEN: EXPAAA</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Animals ; Antibodies, Protozoan - immunology ; apoptosis ; Biological and medical sciences ; Blotting, Western ; Cell Death - immunology ; Cross-Linking Reagents ; DNA Fragmentation ; Fas antigen ; Fas ligand ; Fas receptor ; fas Receptor - immunology ; FasL protein ; FasL, Fas ligand ; FasR protein ; FasR, Fas receptor ; FBS, fetal bovine serum ; Flow Cytometry ; FS, forward scatter ; Fundamental and applied biological sciences. Psychology ; huFasL, human FasL ; Humans ; Life cycle. Host-agent relationship. Pathogenesis ; Ligands ; Microscopy, Fluorescence ; NCC, nonspecific cytotoxic cells ; nonspecific cytotoxic cells ; pathogenic protozoan parasite ; PBL, peripheral blood lymphocytes ; PCD, programmed cell death ; programmed cell death ; Protozoa ; SASF, stress-activated serum factors ; sFasL, soluble FasL ; SSc, side scatter ; Tetrahymena ; Tetrahymena - immunology ; Tilapia ; Tumor Cells, Cultured</subject><ispartof>Experimental parasitology, 2000-10, Vol.96 (2), p.75-88</ispartof><rights>2000 Academic Press</rights><rights>2001 INIST-CNRS</rights><rights>Copyright 2000 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-a82cd4fdf9592289f1ef57948bc9ec4e0720743f9c023f0bc12eabefab0cbc223</citedby><cites>FETCH-LOGICAL-c399t-a82cd4fdf9592289f1ef57948bc9ec4e0720743f9c023f0bc12eabefab0cbc223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/expr.2000.4561$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=815724$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11052866$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jaso-Friedmann, Liliana</creatorcontrib><creatorcontrib>Leary, John H.</creatorcontrib><creatorcontrib>Evans, Donald L.</creatorcontrib><title>Role of Nonspecific Cytotoxic Cells in the Induction of Programmed Cell Death of Pathogenic Protozoans: Participation of the Fas Ligand-Fas Receptor System</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>Jaso-Friedmann, L., Leary, J. H. III, and Evans D. L. 2000. Role of nonspecific cytotoxic cells in the induction of programmed cell death of pathogenic protozoans: Participation of the Fas ligand-Fas receptor system. Experimental Parasitology96, 75–88. Numerous different species of parasites and pathogenic microorganisms produce programmed cell death (PCD) and apoptosis in eukaryotic targets. How ever, only a few studies have demonstrated that effector cells, cytokines, growth factors, or soluble apoptosis-inducing factors are capable of initiating apoptosis in protozoan parasites. Certain Tetrahymena spp. in teleosts are opportunistic pathogens. In the present study these pathogenic protozoans were developed as a model system to describe the potential role of the Fas ligand (FasL)-Fas receptor (FasR) system as a means of innate immunity in teleosts. Nonspecific cytotoxic cells (NCC) constitutively express soluble FasL (sFasL). Binding of the antigen receptor (i.e., NCCRP-1) on NCC to target cells caused the release of sFasL into the milieu. The presence of functional sFasL in these supernatants was determined by Western blot analysis and by demonstrating the lysis of FasR+ HL-60 but not IM-9 (FasR−) targets. Soluble FasL containing supernatants generated by tumor cell-activated NCC also produced a reduction in 2 N DNA (i.e., DNA hypoploidy) of T. furgasoni. The induction of DNA hypoploidy by NCC supernatants could be neutralized by adsorption of the supernatants with anti-FasL antibody (but not with an isotype control). Experiments were next done to determine the expression of FasR on Tetrahymena and study the effects of anti-FasR monoclonal crosslinkage and treatment with soluble human recombinant FasL (huFasL) on initiation of PCD in Tetrahymena. Cell cycle analysis revealed that both crosslinkage and soluble huFasL binding to Tetrahymena produced DNA hypoploidy. The reduction in diploid DNA was confirmed by observing oligonucleosome fragmentation (DNA laddering) following anti-FasR treatment. Additional evidence for FasR expression on Tetrahymena was obtained using fluorescence microscopy and flow cytometry. Both methods showed that all Tetrahymena examined (three species consisting of four isolates) expressed membrane FasR. These studies demonstrated the potential of the FasL-FasR system in teleosts for initiation of antiparasite innate immunity. Effector NCC may initiate PCD of Tetrahymena that express a FasR-like protein. Induction of apoptosis may be a major mechanism of homeostatic control of protozoan parasite infestations/infections.</description><subject>Animals</subject><subject>Antibodies, Protozoan - immunology</subject><subject>apoptosis</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cell Death - immunology</subject><subject>Cross-Linking Reagents</subject><subject>DNA Fragmentation</subject><subject>Fas antigen</subject><subject>Fas ligand</subject><subject>Fas receptor</subject><subject>fas Receptor - immunology</subject><subject>FasL protein</subject><subject>FasL, Fas ligand</subject><subject>FasR protein</subject><subject>FasR, Fas receptor</subject><subject>FBS, fetal bovine serum</subject><subject>Flow Cytometry</subject><subject>FS, forward scatter</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>huFasL, human FasL</subject><subject>Humans</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>Ligands</subject><subject>Microscopy, Fluorescence</subject><subject>NCC, nonspecific cytotoxic cells</subject><subject>nonspecific cytotoxic cells</subject><subject>pathogenic protozoan parasite</subject><subject>PBL, peripheral blood lymphocytes</subject><subject>PCD, programmed cell death</subject><subject>programmed cell death</subject><subject>Protozoa</subject><subject>SASF, stress-activated serum factors</subject><subject>sFasL, soluble FasL</subject><subject>SSc, side scatter</subject><subject>Tetrahymena</subject><subject>Tetrahymena - immunology</subject><subject>Tilapia</subject><subject>Tumor Cells, Cultured</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi0EokvhyhFFQuKWxXacxOaGthQqrQAVOFvOZLw1SuJge1GXV-FlcboLnBCnGdnf_LLnI-Qpo2tGafMSb-ew5pTStagbdo-sGFW05EKo-2RFKROlkEqckUcxfs2UZFw8JGeM0ZrLplmRn9d-wMLb4r2f4ozgrINic0g--dulw2GIhZuKdIPF1dTvITk_LfzH4HfBjCP2d1BxgSbd3F3k6nc45enMJP_Dmym-yschOXCz-R2wJF6aWGzdzkx9ubTXCDgnH4pPh5hwfEweWDNEfHKq5-TL5ZvPm3fl9sPbq83rbQmVUqk0kkMvbG9VrTiXyjK0dauE7EAhCKQtp62orALKK0s7YBxNh9Z0FDrgvDonL465c_Df9hiTHl2E_Ckzod9H3fKqUUxW_wVZ21ZSVHUG10cQgo8xoNVzcKMJB82oXrzpxZtevOnFWx54dkred3mlf_GTqAw8PwEmghlsMBO4-IeTrG65yJQ8UpjX9d1h0BEcToC9CwhJ99796wW_AMI5th0</recordid><startdate>20001001</startdate><enddate>20001001</enddate><creator>Jaso-Friedmann, Liliana</creator><creator>Leary, John H.</creator><creator>Evans, Donald L.</creator><general>Elsevier Inc</general><general>Elsevier</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>7T5</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>20001001</creationdate><title>Role of Nonspecific Cytotoxic Cells in the Induction of Programmed Cell Death of Pathogenic Protozoans: Participation of the Fas Ligand-Fas Receptor System</title><author>Jaso-Friedmann, Liliana ; Leary, John H. ; Evans, Donald L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-a82cd4fdf9592289f1ef57948bc9ec4e0720743f9c023f0bc12eabefab0cbc223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Antibodies, Protozoan - immunology</topic><topic>apoptosis</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cell Death - immunology</topic><topic>Cross-Linking Reagents</topic><topic>DNA Fragmentation</topic><topic>Fas antigen</topic><topic>Fas ligand</topic><topic>Fas receptor</topic><topic>fas Receptor - immunology</topic><topic>FasL protein</topic><topic>FasL, Fas ligand</topic><topic>FasR protein</topic><topic>FasR, Fas receptor</topic><topic>FBS, fetal bovine serum</topic><topic>Flow Cytometry</topic><topic>FS, forward scatter</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>huFasL, human FasL</topic><topic>Humans</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>Ligands</topic><topic>Microscopy, Fluorescence</topic><topic>NCC, nonspecific cytotoxic cells</topic><topic>nonspecific cytotoxic cells</topic><topic>pathogenic protozoan parasite</topic><topic>PBL, peripheral blood lymphocytes</topic><topic>PCD, programmed cell death</topic><topic>programmed cell death</topic><topic>Protozoa</topic><topic>SASF, stress-activated serum factors</topic><topic>sFasL, soluble FasL</topic><topic>SSc, side scatter</topic><topic>Tetrahymena</topic><topic>Tetrahymena - immunology</topic><topic>Tilapia</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jaso-Friedmann, Liliana</creatorcontrib><creatorcontrib>Leary, John H.</creatorcontrib><creatorcontrib>Evans, Donald L.</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jaso-Friedmann, Liliana</au><au>Leary, John H.</au><au>Evans, Donald L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Nonspecific Cytotoxic Cells in the Induction of Programmed Cell Death of Pathogenic Protozoans: Participation of the Fas Ligand-Fas Receptor System</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>2000-10-01</date><risdate>2000</risdate><volume>96</volume><issue>2</issue><spage>75</spage><epage>88</epage><pages>75-88</pages><issn>0014-4894</issn><eissn>1090-2449</eissn><coden>EXPAAA</coden><abstract>Jaso-Friedmann, L., Leary, J. H. III, and Evans D. L. 2000. Role of nonspecific cytotoxic cells in the induction of programmed cell death of pathogenic protozoans: Participation of the Fas ligand-Fas receptor system. Experimental Parasitology96, 75–88. Numerous different species of parasites and pathogenic microorganisms produce programmed cell death (PCD) and apoptosis in eukaryotic targets. How ever, only a few studies have demonstrated that effector cells, cytokines, growth factors, or soluble apoptosis-inducing factors are capable of initiating apoptosis in protozoan parasites. Certain Tetrahymena spp. in teleosts are opportunistic pathogens. In the present study these pathogenic protozoans were developed as a model system to describe the potential role of the Fas ligand (FasL)-Fas receptor (FasR) system as a means of innate immunity in teleosts. Nonspecific cytotoxic cells (NCC) constitutively express soluble FasL (sFasL). Binding of the antigen receptor (i.e., NCCRP-1) on NCC to target cells caused the release of sFasL into the milieu. The presence of functional sFasL in these supernatants was determined by Western blot analysis and by demonstrating the lysis of FasR+ HL-60 but not IM-9 (FasR−) targets. Soluble FasL containing supernatants generated by tumor cell-activated NCC also produced a reduction in 2 N DNA (i.e., DNA hypoploidy) of T. furgasoni. The induction of DNA hypoploidy by NCC supernatants could be neutralized by adsorption of the supernatants with anti-FasL antibody (but not with an isotype control). Experiments were next done to determine the expression of FasR on Tetrahymena and study the effects of anti-FasR monoclonal crosslinkage and treatment with soluble human recombinant FasL (huFasL) on initiation of PCD in Tetrahymena. Cell cycle analysis revealed that both crosslinkage and soluble huFasL binding to Tetrahymena produced DNA hypoploidy. The reduction in diploid DNA was confirmed by observing oligonucleosome fragmentation (DNA laddering) following anti-FasR treatment. Additional evidence for FasR expression on Tetrahymena was obtained using fluorescence microscopy and flow cytometry. Both methods showed that all Tetrahymena examined (three species consisting of four isolates) expressed membrane FasR. These studies demonstrated the potential of the FasL-FasR system in teleosts for initiation of antiparasite innate immunity. Effector NCC may initiate PCD of Tetrahymena that express a FasR-like protein. Induction of apoptosis may be a major mechanism of homeostatic control of protozoan parasite infestations/infections.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>11052866</pmid><doi>10.1006/expr.2000.4561</doi><tpages>14</tpages></addata></record>
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subjects Animals
Antibodies, Protozoan - immunology
apoptosis
Biological and medical sciences
Blotting, Western
Cell Death - immunology
Cross-Linking Reagents
DNA Fragmentation
Fas antigen
Fas ligand
Fas receptor
fas Receptor - immunology
FasL protein
FasL, Fas ligand
FasR protein
FasR, Fas receptor
FBS, fetal bovine serum
Flow Cytometry
FS, forward scatter
Fundamental and applied biological sciences. Psychology
huFasL, human FasL
Humans
Life cycle. Host-agent relationship. Pathogenesis
Ligands
Microscopy, Fluorescence
NCC, nonspecific cytotoxic cells
nonspecific cytotoxic cells
pathogenic protozoan parasite
PBL, peripheral blood lymphocytes
PCD, programmed cell death
programmed cell death
Protozoa
SASF, stress-activated serum factors
sFasL, soluble FasL
SSc, side scatter
Tetrahymena
Tetrahymena - immunology
Tilapia
Tumor Cells, Cultured
title Role of Nonspecific Cytotoxic Cells in the Induction of Programmed Cell Death of Pathogenic Protozoans: Participation of the Fas Ligand-Fas Receptor System
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