Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses
Infusion of human third-party mesenchymal stromal cells (MSCs) appears to be a promising therapy for acute graft-versus-host disease (aGvHD). To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to...
Gespeichert in:
| Veröffentlicht in: | PloS one 2011-07, Vol.6 (7), p.e21703-e21703 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e21703 |
|---|---|
| container_issue | 7 |
| container_start_page | e21703 |
| container_title | PloS one |
| container_volume | 6 |
| creator | Moll, Guido Jitschin, Regina von Bahr, Lena Rasmusson-Duprez, Ida Sundberg, Berit Lönnies, Lena Elgue, Graciela Nilsson-Ekdahl, Kristina Mougiakakos, Dimitrios Lambris, John D Ringdén, Olle Le Blanc, Katarina Nilsson, Bo |
| description | Infusion of human third-party mesenchymal stromal cells (MSCs) appears to be a promising therapy for acute graft-versus-host disease (aGvHD). To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46) and DAF (CD55), but were protected from complement lysis via expression of protectin (CD59). Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18)-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells. |
| doi_str_mv | 10.1371/journal.pone.0021703 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1305137585</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A476886421</galeid><doaj_id>oai_doaj_org_article_46ae7b796f7f4a8f99da2276c4e3c919</doaj_id><sourcerecordid>A476886421</sourcerecordid><originalsourceid>FETCH-LOGICAL-c869t-cfc5fd16d386a7580bc95f54d86f154bbe02d6b08aaca0eedea1da59c63f1e373</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7rr6D0QLgiI4Y9I0aXsjLOvXwMqCH3sb0vSkkzFNxqRV98bfbrrTXaaywtKLJCfPeU_6JidJHmO0xKTArzdu8FaY5dZZWCKU4QKRO8khrki2YBkid_fmB8mDEDYIUVIydj85iHBeVHl1mPz5BAGsXF90wqSh924cJRgTUrCtaCGVrtsa6MD2qbDN_tKDhG3vfFqD8Nq2qbZW9JCCUiDH-E6nd2nnmsGMW7rrBgsxM8RjBwgPk3tKmACPpvEo-fb-3deTj4vTsw-rk-PThSxZ1S-kklQ1mDXx_KKgJaplRRXNm5IpTPO6BpQ1rEalEFIggAYEbgStJCMKAynIUfJ0p7s1LvDJusAxQTSaSUsaidWOaJzY8K3XnfAX3AnNLwPOt1z4XksDPGcCirqomCpULkpVVY3IsoLJHIisoulHyWKnFX7BdqhnalPoe5wBpznBDEX-1X_5t_r8-LL6MHBMWZaR2-HGRr6sqizib6Z_H-oOGhmvzgszy5rvWL3mrfvJCc5KhnEUeDEJePdjgNDzTofxboUFNwReFizLMcWjzc_-IW-2eqJaEd3UVrlYVo6a_DgvWFmyPBurLm-g4tdAp2V89ErH-Czh5SwhMj387lsxhMBXXz7fnj07n7PP99g1CNOvgzNDr-MTnoP5DpTeheBBXXuMER979soNPvYsn3o2pj3Zv5_rpKsmJX8BFN5A3Q</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1305137585</pqid></control><display><type>article</type><title>Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>SWEPUB Freely available online</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Moll, Guido ; Jitschin, Regina ; von Bahr, Lena ; Rasmusson-Duprez, Ida ; Sundberg, Berit ; Lönnies, Lena ; Elgue, Graciela ; Nilsson-Ekdahl, Kristina ; Mougiakakos, Dimitrios ; Lambris, John D ; Ringdén, Olle ; Le Blanc, Katarina ; Nilsson, Bo</creator><creatorcontrib>Moll, Guido ; Jitschin, Regina ; von Bahr, Lena ; Rasmusson-Duprez, Ida ; Sundberg, Berit ; Lönnies, Lena ; Elgue, Graciela ; Nilsson-Ekdahl, Kristina ; Mougiakakos, Dimitrios ; Lambris, John D ; Ringdén, Olle ; Le Blanc, Katarina ; Nilsson, Bo</creatorcontrib><description>Infusion of human third-party mesenchymal stromal cells (MSCs) appears to be a promising therapy for acute graft-versus-host disease (aGvHD). To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46) and DAF (CD55), but were protected from complement lysis via expression of protectin (CD59). Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18)-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0021703</identifier><identifier>PMID: 21747949</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>ABO system ; Anaphylatoxins ; Animals ; Apoptosis ; Biology ; Blood ; Blood groups ; CD11b antigen ; CD14 antigen ; CD18 antigen ; CD46 antigen ; CD59 antigen ; Cell activation ; Cell surface ; Complement ; Complement activation ; Complement component C3 ; Complement component C5a ; Complement receptor 3 ; Complement regulatory proteins ; Complement System Proteins - metabolism ; Cytokines ; Disease ; Effector cells ; Endothelial Cells - immunology ; Endothelial Cells - metabolism ; Graft-versus-host reaction ; Hematology ; Hospitals ; Human behavior ; Humans ; Immune response ; Immune system ; Immunity, Innate ; Immunoglobulins ; Immunologi ; Immunology ; Immunomodulation ; Immunosuppression ; Infusion ; Innate immunity ; Laboratories ; Lymphocytes ; Lysis ; MEDICIN ; MEDICINE ; Mesenchymal stem cells ; Mesenchyme ; Mesoderm - cytology ; Opsonization ; Pathology ; Peripheral blood mononuclear cells ; Proteins ; Receptors, Complement - metabolism ; Rodents ; Stem cells ; Stromal Cells - immunology ; Stromal Cells - metabolism ; Trends</subject><ispartof>PloS one, 2011-07, Vol.6 (7), p.e21703-e21703</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Moll et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Moll et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c869t-cfc5fd16d386a7580bc95f54d86f154bbe02d6b08aaca0eedea1da59c63f1e373</citedby><cites>FETCH-LOGICAL-c869t-cfc5fd16d386a7580bc95f54d86f154bbe02d6b08aaca0eedea1da59c63f1e373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128611/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128611/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21747949$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-18992$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-156223$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:122870631$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Moll, Guido</creatorcontrib><creatorcontrib>Jitschin, Regina</creatorcontrib><creatorcontrib>von Bahr, Lena</creatorcontrib><creatorcontrib>Rasmusson-Duprez, Ida</creatorcontrib><creatorcontrib>Sundberg, Berit</creatorcontrib><creatorcontrib>Lönnies, Lena</creatorcontrib><creatorcontrib>Elgue, Graciela</creatorcontrib><creatorcontrib>Nilsson-Ekdahl, Kristina</creatorcontrib><creatorcontrib>Mougiakakos, Dimitrios</creatorcontrib><creatorcontrib>Lambris, John D</creatorcontrib><creatorcontrib>Ringdén, Olle</creatorcontrib><creatorcontrib>Le Blanc, Katarina</creatorcontrib><creatorcontrib>Nilsson, Bo</creatorcontrib><title>Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Infusion of human third-party mesenchymal stromal cells (MSCs) appears to be a promising therapy for acute graft-versus-host disease (aGvHD). To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46) and DAF (CD55), but were protected from complement lysis via expression of protectin (CD59). Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18)-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells.</description><subject>ABO system</subject><subject>Anaphylatoxins</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Blood</subject><subject>Blood groups</subject><subject>CD11b antigen</subject><subject>CD14 antigen</subject><subject>CD18 antigen</subject><subject>CD46 antigen</subject><subject>CD59 antigen</subject><subject>Cell activation</subject><subject>Cell surface</subject><subject>Complement</subject><subject>Complement activation</subject><subject>Complement component C3</subject><subject>Complement component C5a</subject><subject>Complement receptor 3</subject><subject>Complement regulatory proteins</subject><subject>Complement System Proteins - metabolism</subject><subject>Cytokines</subject><subject>Disease</subject><subject>Effector cells</subject><subject>Endothelial Cells - immunology</subject><subject>Endothelial Cells - metabolism</subject><subject>Graft-versus-host reaction</subject><subject>Hematology</subject><subject>Hospitals</subject><subject>Human behavior</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity, Innate</subject><subject>Immunoglobulins</subject><subject>Immunologi</subject><subject>Immunology</subject><subject>Immunomodulation</subject><subject>Immunosuppression</subject><subject>Infusion</subject><subject>Innate immunity</subject><subject>Laboratories</subject><subject>Lymphocytes</subject><subject>Lysis</subject><subject>MEDICIN</subject><subject>MEDICINE</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchyme</subject><subject>Mesoderm - cytology</subject><subject>Opsonization</subject><subject>Pathology</subject><subject>Peripheral blood mononuclear cells</subject><subject>Proteins</subject><subject>Receptors, Complement - metabolism</subject><subject>Rodents</subject><subject>Stem cells</subject><subject>Stromal Cells - immunology</subject><subject>Stromal Cells - metabolism</subject><subject>Trends</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>D8T</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgiI4Y9I0aXsjLOvXwMqCH3sb0vSkkzFNxqRV98bfbrrTXaaywtKLJCfPeU_6JidJHmO0xKTArzdu8FaY5dZZWCKU4QKRO8khrki2YBkid_fmB8mDEDYIUVIydj85iHBeVHl1mPz5BAGsXF90wqSh924cJRgTUrCtaCGVrtsa6MD2qbDN_tKDhG3vfFqD8Nq2qbZW9JCCUiDH-E6nd2nnmsGMW7rrBgsxM8RjBwgPk3tKmACPpvEo-fb-3deTj4vTsw-rk-PThSxZ1S-kklQ1mDXx_KKgJaplRRXNm5IpTPO6BpQ1rEalEFIggAYEbgStJCMKAynIUfJ0p7s1LvDJusAxQTSaSUsaidWOaJzY8K3XnfAX3AnNLwPOt1z4XksDPGcCirqomCpULkpVVY3IsoLJHIisoulHyWKnFX7BdqhnalPoe5wBpznBDEX-1X_5t_r8-LL6MHBMWZaR2-HGRr6sqizib6Z_H-oOGhmvzgszy5rvWL3mrfvJCc5KhnEUeDEJePdjgNDzTofxboUFNwReFizLMcWjzc_-IW-2eqJaEd3UVrlYVo6a_DgvWFmyPBurLm-g4tdAp2V89ErH-Czh5SwhMj387lsxhMBXXz7fnj07n7PP99g1CNOvgzNDr-MTnoP5DpTeheBBXXuMER979soNPvYsn3o2pj3Zv5_rpKsmJX8BFN5A3Q</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Moll, Guido</creator><creator>Jitschin, Regina</creator><creator>von Bahr, Lena</creator><creator>Rasmusson-Duprez, Ida</creator><creator>Sundberg, Berit</creator><creator>Lönnies, Lena</creator><creator>Elgue, Graciela</creator><creator>Nilsson-Ekdahl, Kristina</creator><creator>Mougiakakos, Dimitrios</creator><creator>Lambris, John D</creator><creator>Ringdén, Olle</creator><creator>Le Blanc, Katarina</creator><creator>Nilsson, Bo</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D92</scope><scope>DF2</scope><scope>D8T</scope><scope>ZZAVC</scope><scope>DOA</scope></search><sort><creationdate>20110701</creationdate><title>Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses</title><author>Moll, Guido ; Jitschin, Regina ; von Bahr, Lena ; Rasmusson-Duprez, Ida ; Sundberg, Berit ; Lönnies, Lena ; Elgue, Graciela ; Nilsson-Ekdahl, Kristina ; Mougiakakos, Dimitrios ; Lambris, John D ; Ringdén, Olle ; Le Blanc, Katarina ; Nilsson, Bo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c869t-cfc5fd16d386a7580bc95f54d86f154bbe02d6b08aaca0eedea1da59c63f1e373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>ABO system</topic><topic>Anaphylatoxins</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biology</topic><topic>Blood</topic><topic>Blood groups</topic><topic>CD11b antigen</topic><topic>CD14 antigen</topic><topic>CD18 antigen</topic><topic>CD46 antigen</topic><topic>CD59 antigen</topic><topic>Cell activation</topic><topic>Cell surface</topic><topic>Complement</topic><topic>Complement activation</topic><topic>Complement component C3</topic><topic>Complement component C5a</topic><topic>Complement receptor 3</topic><topic>Complement regulatory proteins</topic><topic>Complement System Proteins - metabolism</topic><topic>Cytokines</topic><topic>Disease</topic><topic>Effector cells</topic><topic>Endothelial Cells - immunology</topic><topic>Endothelial Cells - metabolism</topic><topic>Graft-versus-host reaction</topic><topic>Hematology</topic><topic>Hospitals</topic><topic>Human behavior</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunity, Innate</topic><topic>Immunoglobulins</topic><topic>Immunologi</topic><topic>Immunology</topic><topic>Immunomodulation</topic><topic>Immunosuppression</topic><topic>Infusion</topic><topic>Innate immunity</topic><topic>Laboratories</topic><topic>Lymphocytes</topic><topic>Lysis</topic><topic>MEDICIN</topic><topic>MEDICINE</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchyme</topic><topic>Mesoderm - cytology</topic><topic>Opsonization</topic><topic>Pathology</topic><topic>Peripheral blood mononuclear cells</topic><topic>Proteins</topic><topic>Receptors, Complement - metabolism</topic><topic>Rodents</topic><topic>Stem cells</topic><topic>Stromal Cells - immunology</topic><topic>Stromal Cells - metabolism</topic><topic>Trends</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moll, Guido</creatorcontrib><creatorcontrib>Jitschin, Regina</creatorcontrib><creatorcontrib>von Bahr, Lena</creatorcontrib><creatorcontrib>Rasmusson-Duprez, Ida</creatorcontrib><creatorcontrib>Sundberg, Berit</creatorcontrib><creatorcontrib>Lönnies, Lena</creatorcontrib><creatorcontrib>Elgue, Graciela</creatorcontrib><creatorcontrib>Nilsson-Ekdahl, Kristina</creatorcontrib><creatorcontrib>Mougiakakos, Dimitrios</creatorcontrib><creatorcontrib>Lambris, John D</creatorcontrib><creatorcontrib>Ringdén, Olle</creatorcontrib><creatorcontrib>Le Blanc, Katarina</creatorcontrib><creatorcontrib>Nilsson, Bo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Linnéuniversitetet</collection><collection>SWEPUB Uppsala universitet</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moll, Guido</au><au>Jitschin, Regina</au><au>von Bahr, Lena</au><au>Rasmusson-Duprez, Ida</au><au>Sundberg, Berit</au><au>Lönnies, Lena</au><au>Elgue, Graciela</au><au>Nilsson-Ekdahl, Kristina</au><au>Mougiakakos, Dimitrios</au><au>Lambris, John D</au><au>Ringdén, Olle</au><au>Le Blanc, Katarina</au><au>Nilsson, Bo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>6</volume><issue>7</issue><spage>e21703</spage><epage>e21703</epage><pages>e21703-e21703</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Infusion of human third-party mesenchymal stromal cells (MSCs) appears to be a promising therapy for acute graft-versus-host disease (aGvHD). To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46) and DAF (CD55), but were protected from complement lysis via expression of protectin (CD59). Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18)-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21747949</pmid><doi>10.1371/journal.pone.0021703</doi><tpages>e21703</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-07, Vol.6 (7), p.e21703-e21703 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1305137585 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SWEPUB Freely available online; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | ABO system Anaphylatoxins Animals Apoptosis Biology Blood Blood groups CD11b antigen CD14 antigen CD18 antigen CD46 antigen CD59 antigen Cell activation Cell surface Complement Complement activation Complement component C3 Complement component C5a Complement receptor 3 Complement regulatory proteins Complement System Proteins - metabolism Cytokines Disease Effector cells Endothelial Cells - immunology Endothelial Cells - metabolism Graft-versus-host reaction Hematology Hospitals Human behavior Humans Immune response Immune system Immunity, Innate Immunoglobulins Immunologi Immunology Immunomodulation Immunosuppression Infusion Innate immunity Laboratories Lymphocytes Lysis MEDICIN MEDICINE Mesenchymal stem cells Mesenchyme Mesoderm - cytology Opsonization Pathology Peripheral blood mononuclear cells Proteins Receptors, Complement - metabolism Rodents Stem cells Stromal Cells - immunology Stromal Cells - metabolism Trends |
| title | Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T14%3A15%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mesenchymal%20stromal%20cells%20engage%20complement%20and%20complement%20receptor%20bearing%20innate%20effector%20cells%20to%20modulate%20immune%20responses&rft.jtitle=PloS%20one&rft.au=Moll,%20Guido&rft.date=2011-07-01&rft.volume=6&rft.issue=7&rft.spage=e21703&rft.epage=e21703&rft.pages=e21703-e21703&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0021703&rft_dat=%3Cgale_plos_%3EA476886421%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1305137585&rft_id=info:pmid/21747949&rft_galeid=A476886421&rft_doaj_id=oai_doaj_org_article_46ae7b796f7f4a8f99da2276c4e3c919&rfr_iscdi=true |