Platelet Factor 4 and Duffy Antigen Required for Platelet Killing of Plasmodium falciparum
Platelets restrict the growth of intraerythrocytic malaria parasites by binding to parasitized cells and killing the parasite within. Here, we show that the platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) are necessary for platelet-mediated killing...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2012-12, Vol.338 (6112), p.1348-1351 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | McMorran, Brendan J. Wieczorski, Laura Drysdale, Karen E. Chan, Jo-Anne Huang, Hong Ming Smith, Clare Mitiku, Chalachew Beeson, James G. Burgio, Gaetan Foote, Simon J. |
| description | Platelets restrict the growth of intraerythrocytic malaria parasites by binding to parasitized cells and killing the parasite within. Here, we show that the platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) are necessary for platelet-mediated killing of Plasmodium falciparum parasites. PF4 is released by platelets on contact with parasitized red cells, and the protein directly kills intraerythrocytic parasites. This function for PF4 is critically dependent on Fy, which binds PF4. Genetic disruption of Fy expression inhibits binding of PF4 to parasitized cells and concomitantly prevents parasite killing by both human platelets and recombinant human PF4. The protective function afforded by platelets during a malarial infection may therefore be compromised in Duffy-negative individuals, who do not express Fy. |
| doi_str_mv | 10.1126/science.1228892 |
| format | Article |
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Here, we show that the platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) are necessary for platelet-mediated killing of Plasmodium falciparum parasites. PF4 is released by platelets on contact with parasitized red cells, and the protein directly kills intraerythrocytic parasites. This function for PF4 is critically dependent on Fy, which binds PF4. Genetic disruption of Fy expression inhibits binding of PF4 to parasitized cells and concomitantly prevents parasite killing by both human platelets and recombinant human PF4. The protective function afforded by platelets during a malarial infection may therefore be compromised in Duffy-negative individuals, who do not express Fy.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1228892</identifier><identifier>PMID: 23224555</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Antibodies ; Antigens ; Biological and medical sciences ; Blood platelets ; Blood Platelets - immunology ; Cells, Cultured ; Chemokines ; Duffy Blood-Group System - genetics ; Duffy Blood-Group System - immunology ; Erythrocytes ; Erythrocytes - parasitology ; Granular materials ; Human protozoal diseases ; Humans ; Immune system ; Infections ; Infectious diseases ; Malaria ; Malaria, Falciparum - blood ; Malaria, Falciparum - immunology ; Malaria, Falciparum - parasitology ; Medical research ; Medical sciences ; Molecules ; Parasites ; Parasitic diseases ; Parasitic protozoa ; Parasitism ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - growth & development ; Plasmodium falciparum - immunology ; Platelet Factor 4 - genetics ; Platelet Factor 4 - immunology ; Platelet Factor 4 - pharmacology ; Platelets ; Poisons ; Proteins ; Protozoal diseases ; Receptors ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - immunology ; Recombinant Proteins - pharmacology ; Red blood cells ; Trophozoites</subject><ispartof>Science (American Association for the Advancement of Science), 2012-12, Vol.338 (6112), p.1348-1351</ispartof><rights>Copyright © 2012 American Association for the Advancement of Science</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-1a55a99afe6b2e5d569d2df7f7b22879cf9ad546aaa921f8245b88e21104c0363</citedby><cites>FETCH-LOGICAL-c443t-1a55a99afe6b2e5d569d2df7f7b22879cf9ad546aaa921f8245b88e21104c0363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/23332017$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/23332017$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2870,2871,27903,27904,57996,58229</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26791090$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23224555$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McMorran, Brendan J.</creatorcontrib><creatorcontrib>Wieczorski, Laura</creatorcontrib><creatorcontrib>Drysdale, Karen E.</creatorcontrib><creatorcontrib>Chan, Jo-Anne</creatorcontrib><creatorcontrib>Huang, Hong Ming</creatorcontrib><creatorcontrib>Smith, Clare</creatorcontrib><creatorcontrib>Mitiku, Chalachew</creatorcontrib><creatorcontrib>Beeson, James G.</creatorcontrib><creatorcontrib>Burgio, Gaetan</creatorcontrib><creatorcontrib>Foote, Simon J.</creatorcontrib><title>Platelet Factor 4 and Duffy Antigen Required for Platelet Killing of Plasmodium falciparum</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Platelets restrict the growth of intraerythrocytic malaria parasites by binding to parasitized cells and killing the parasite within. Here, we show that the platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) are necessary for platelet-mediated killing of Plasmodium falciparum parasites. PF4 is released by platelets on contact with parasitized red cells, and the protein directly kills intraerythrocytic parasites. This function for PF4 is critically dependent on Fy, which binds PF4. Genetic disruption of Fy expression inhibits binding of PF4 to parasitized cells and concomitantly prevents parasite killing by both human platelets and recombinant human PF4. The protective function afforded by platelets during a malarial infection may therefore be compromised in Duffy-negative individuals, who do not express Fy.</description><subject>Antibodies</subject><subject>Antigens</subject><subject>Biological and medical sciences</subject><subject>Blood platelets</subject><subject>Blood Platelets - immunology</subject><subject>Cells, Cultured</subject><subject>Chemokines</subject><subject>Duffy Blood-Group System - genetics</subject><subject>Duffy Blood-Group System - immunology</subject><subject>Erythrocytes</subject><subject>Erythrocytes - parasitology</subject><subject>Granular materials</subject><subject>Human protozoal diseases</subject><subject>Humans</subject><subject>Immune system</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Malaria</subject><subject>Malaria, Falciparum - blood</subject><subject>Malaria, Falciparum - immunology</subject><subject>Malaria, Falciparum - parasitology</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Molecules</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Parasitic protozoa</subject><subject>Parasitism</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - growth & development</subject><subject>Plasmodium falciparum - immunology</subject><subject>Platelet Factor 4 - genetics</subject><subject>Platelet Factor 4 - immunology</subject><subject>Platelet Factor 4 - pharmacology</subject><subject>Platelets</subject><subject>Poisons</subject><subject>Proteins</subject><subject>Protozoal diseases</subject><subject>Receptors</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - immunology</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Red blood cells</subject><subject>Trophozoites</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0k1rFTEUBuAgir2trl0pARHcTJucfC9LtVUsKKIbN8O5maTkMh-3ycyi_96UO1Zx01VI8pxDDm8IecXZKeegz4pPYfThlANY6-AJ2XDmVOOAiadkw5jQjWVGHZHjUnaM1TsnnpMjEABSKbUhv771OIc-zPQS_TxlKimOHf2wxHhHz8c53YSRfg-3S8qho7GCh4Ivqe_TeEOneH9WhqlLy0Aj9j7tMS_DC_Ksbkp4ua4n5Oflxx8Xn5rrr1efL86vGy-lmBuOSqFzGIPeQlCd0q6DLppotnUo43x02CmpEdEBj7Y-fGttAM6Z9HVAcULeH_ru83S7hDK3Qyo-9D2OYVpKyy2zHISS7nGqFNeCWwOPUxBGMaWlqfTtf3Q3LXmsM1cFQlrOtKjq7KB8nkrJIbb7nAbMdy1n7X2Y7Rpmu4ZZK96sfZftELoH_ye9Ct6tAIvHPmYcfSp_nTaufgdW3euD25Ua8T99hADGjfgN-1av0w</recordid><startdate>20121207</startdate><enddate>20121207</enddate><creator>McMorran, Brendan J.</creator><creator>Wieczorski, Laura</creator><creator>Drysdale, Karen E.</creator><creator>Chan, Jo-Anne</creator><creator>Huang, Hong Ming</creator><creator>Smith, Clare</creator><creator>Mitiku, Chalachew</creator><creator>Beeson, James G.</creator><creator>Burgio, Gaetan</creator><creator>Foote, Simon J.</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of 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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope></search><sort><creationdate>20121207</creationdate><title>Platelet Factor 4 and Duffy Antigen Required for Platelet Killing of Plasmodium falciparum</title><author>McMorran, Brendan J. ; Wieczorski, Laura ; Drysdale, Karen E. ; Chan, Jo-Anne ; Huang, Hong Ming ; Smith, Clare ; Mitiku, Chalachew ; Beeson, James G. ; Burgio, Gaetan ; Foote, Simon J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-1a55a99afe6b2e5d569d2df7f7b22879cf9ad546aaa921f8245b88e21104c0363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Antibodies</topic><topic>Antigens</topic><topic>Biological and medical sciences</topic><topic>Blood platelets</topic><topic>Blood Platelets - immunology</topic><topic>Cells, Cultured</topic><topic>Chemokines</topic><topic>Duffy Blood-Group System - genetics</topic><topic>Duffy Blood-Group System - immunology</topic><topic>Erythrocytes</topic><topic>Erythrocytes - parasitology</topic><topic>Granular materials</topic><topic>Human protozoal diseases</topic><topic>Humans</topic><topic>Immune system</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Malaria</topic><topic>Malaria, Falciparum - blood</topic><topic>Malaria, Falciparum - immunology</topic><topic>Malaria, Falciparum - parasitology</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Molecules</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Parasitic protozoa</topic><topic>Parasitism</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - growth & development</topic><topic>Plasmodium falciparum - immunology</topic><topic>Platelet Factor 4 - genetics</topic><topic>Platelet Factor 4 - immunology</topic><topic>Platelet Factor 4 - pharmacology</topic><topic>Platelets</topic><topic>Poisons</topic><topic>Proteins</topic><topic>Protozoal diseases</topic><topic>Receptors</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - immunology</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Red blood cells</topic><topic>Trophozoites</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McMorran, Brendan J.</creatorcontrib><creatorcontrib>Wieczorski, Laura</creatorcontrib><creatorcontrib>Drysdale, Karen E.</creatorcontrib><creatorcontrib>Chan, Jo-Anne</creatorcontrib><creatorcontrib>Huang, Hong Ming</creatorcontrib><creatorcontrib>Smith, Clare</creatorcontrib><creatorcontrib>Mitiku, Chalachew</creatorcontrib><creatorcontrib>Beeson, James G.</creatorcontrib><creatorcontrib>Burgio, Gaetan</creatorcontrib><creatorcontrib>Foote, Simon J.</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>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McMorran, Brendan J.</au><au>Wieczorski, Laura</au><au>Drysdale, Karen E.</au><au>Chan, Jo-Anne</au><au>Huang, Hong Ming</au><au>Smith, Clare</au><au>Mitiku, Chalachew</au><au>Beeson, James G.</au><au>Burgio, Gaetan</au><au>Foote, Simon J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Platelet Factor 4 and Duffy Antigen Required for Platelet Killing of Plasmodium falciparum</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2012-12-07</date><risdate>2012</risdate><volume>338</volume><issue>6112</issue><spage>1348</spage><epage>1351</epage><pages>1348-1351</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Platelets restrict the growth of intraerythrocytic malaria parasites by binding to parasitized cells and killing the parasite within. Here, we show that the platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) are necessary for platelet-mediated killing of Plasmodium falciparum parasites. PF4 is released by platelets on contact with parasitized red cells, and the protein directly kills intraerythrocytic parasites. This function for PF4 is critically dependent on Fy, which binds PF4. Genetic disruption of Fy expression inhibits binding of PF4 to parasitized cells and concomitantly prevents parasite killing by both human platelets and recombinant human PF4. The protective function afforded by platelets during a malarial infection may therefore be compromised in Duffy-negative individuals, who do not express Fy.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>23224555</pmid><doi>10.1126/science.1228892</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Science (American Association for the Advancement of Science), 2012-12, Vol.338 (6112), p.1348-1351 |
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| subjects | Antibodies Antigens Biological and medical sciences Blood platelets Blood Platelets - immunology Cells, Cultured Chemokines Duffy Blood-Group System - genetics Duffy Blood-Group System - immunology Erythrocytes Erythrocytes - parasitology Granular materials Human protozoal diseases Humans Immune system Infections Infectious diseases Malaria Malaria, Falciparum - blood Malaria, Falciparum - immunology Malaria, Falciparum - parasitology Medical research Medical sciences Molecules Parasites Parasitic diseases Parasitic protozoa Parasitism Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - growth & development Plasmodium falciparum - immunology Platelet Factor 4 - genetics Platelet Factor 4 - immunology Platelet Factor 4 - pharmacology Platelets Poisons Proteins Protozoal diseases Receptors Receptors, Cell Surface - genetics Receptors, Cell Surface - immunology Recombinant Proteins - pharmacology Red blood cells Trophozoites |
| title | Platelet Factor 4 and Duffy Antigen Required for Platelet Killing of Plasmodium falciparum |
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