{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:14:22Z","timestamp":1791490462234,"version":"4.3.4"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,1,22]]},"abstract":"<jats:p>\n                    Sickle trait, the heterozygous state of normal hemoglobin A (HbA) and sickle hemoglobin S (HbS), confers protection against malaria in Africa. AS children infected with\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    are less likely than AA children to suffer the symptoms or severe manifestations of malaria, and they often carry lower parasite densities than AA children. The mechanisms by which sickle trait might confer such malaria protection remain unclear. We have compared the cytoadherence properties of parasitized AS and AA erythrocytes, because it is by these properties that parasitized erythrocytes can sequester in postcapillary microvessels of critical tissues such as the brain and cause the life-threatening complications of malaria. Our results show that the binding of parasitized AS erythrocytes to microvascular endothelial cells and blood monocytes is significantly reduced relative to the binding of parasitized AA erythrocytes. Reduced binding correlates with the altered display of\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    erythrocyte membrane protein-1 (PfEMP-1), the parasite's major cytoadherence ligand and virulence factor on the erythrocyte surface. These findings identify a mechanism of protection for HbS that has features in common with that of hemoglobin C (HbC). Coinherited hemoglobin polymorphisms and naturally acquired antibodies to PfEMP-1 may influence the degree of malaria protection in AS children by further weakening cytoadherence interactions.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0711401105","type":"journal-article","created":{"date-parts":[[2008,1,11]],"date-time":"2008-01-11T20:53:52Z","timestamp":1200084832000},"page":"991-996","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":225,"title":["Impaired cytoadherence of\n                    <i>Plasmodium falciparum<\/i>\n                    -infected erythrocytes containing sickle hemoglobin"],"prefix":"10.1073","volume":"105","author":[{"given":"Rushina","family":"Cholera","sequence":"first","affiliation":[{"name":"*Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel J.","family":"Brittain","sequence":"additional","affiliation":[{"name":"*Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Gillrie","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana M.","family":"Lopera-Mesa","sequence":"additional","affiliation":[{"name":"*Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9idina A. S.","family":"Diakit\u00e9","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Bamako, Bamako, BP 1805, Mali; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Arie","sequence":"additional","affiliation":[{"name":"*Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Krause","sequence":"additional","affiliation":[{"name":"*Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldiouma","family":"Guindo","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Bamako, Bamako, BP 1805, Mali; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby","family":"Tubman","sequence":"additional","affiliation":[{"name":"*Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Fujioka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapa A.","family":"Diallo","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Bamako, Bamako, BP 1805, Mali; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ogobara K.","family":"Doumbo","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Bamako, Bamako, BP 1805, Mali; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Wellems","sequence":"additional","affiliation":[{"name":"*Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick M.","family":"Fairhurst","sequence":"additional","affiliation":[{"name":"*Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,1,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4857.290"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/SQB.1964.029.01.018"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/430744"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/352595a0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08273-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.20.2220"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/02724936.1997.11747877"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2003.10.001"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020128"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(70)90700-2"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.4.1994"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/274701a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-11-3820"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.11.3909.bloodjournal84113909"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.7.2358"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1660"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4923.1189"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/35104556"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/422847"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03631"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.6.2323-2326.1995"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)93174-N"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90054-3"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90056-X"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90055-1"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65136-X"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80207-X"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2467377"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114188"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.9.3231"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/415673a"},{"key":"e_1_3_3_32_2","first-page":"1057","article-title":"An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration.","volume":"145","author":"Turner GD","year":"1994","unstructured":"GD Turner, et al., An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol 145, 1057\u20131069 (1994).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2003.10.004"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.3.812.812"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198906153202404"},{"key":"e_1_3_3_36_2","first-page":"385","article-title":"Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration.","volume":"119","author":"MacPherson GG","year":"1985","unstructured":"GG MacPherson, MJ Warrell, NJ White, S Looareesuwan, DA Warrell, Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol 119, 385\u2013401 (1985).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02381"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2005.02.008"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06446.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)68308-5"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1978.11719283"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.6.2292"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0711401105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:51:23Z","timestamp":1649782283000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0711401105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,22]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,1,22]]}},"alternative-id":["10.1073\/pnas.0711401105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0711401105","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1100128.556288","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,22]]},"assertion":[{"value":"2007-08-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-01-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}