{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T23:43:40Z","timestamp":1774050220414,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a deadly complication of malaria, and its pathophysiology is insufficiently understood. Both in humans and in murine models, MA-ARDS is characterized by marked pulmonary inflammation. We investigated the role of hemozoin in MA-ARDS in C57Bl\/6 mice infected with Plasmodium berghei NK65, P. berghei ANKA, and P. chabaudi AS. By quantifying hemozoin in the lungs and measuring the disease parameters of MA-ARDS, we demonstrated a highly significant correlation between pulmonary hemozoin concentrations, lung weights, and alveolar edema. Histological analysis of the lungs demonstrated that hemozoin is localized in phagocytes and infected erythrocytes, and only occasionally in granulocytes. Species-specific differences in hemozoin production, as measured among individual schizonts, were associated with variations in pulmonary pathogenicity. Furthermore, both pulmonary hemozoin and lung pathology were correlated with the number of infiltrating inflammatory cells, an increased pulmonary expression of cytokines, chemokines, and enzymes, and concentrations of alveolar vascular endothelial growth factor. The causal relationship between hemozoin and inflammation was investigated by injecting P. falciparum\u2013derived hemozoin intravenously into malaria-free mice. Hemozoin potently induced the pulmonary expression of proinflammatory chemokines (interferon-\u03b3 inducible protein\u201310\/CXC-chemokine ligand (CXCL)10, monocyte chemotactic protein\u20131\/CC-chemokine ligand 2, and keratinocyte-derived chemokine\/CXCL1), cytokines (IL-1\u03b2, IL-6, IL-10, TNF, and transforming growth factor\u2013\u03b2), and other inflammatory mediators (inducible nitric oxide synthase, heme oxygenase\u20131, nicotinamide adenine dinucleotide phosphate\u2013 oxidase\u20132, and intercellular adhesion molecule\u20131). Thus, hemozoin correlates with MA-ARDS and induces pulmonary inflammation.<\/jats:p>","DOI":"10.1165\/rcmb.2012-0450oc","type":"journal-article","created":{"date-parts":[[2013,1,17]],"date-time":"2013-01-17T21:12:04Z","timestamp":1358457124000},"page":"589-600","source":"Crossref","is-referenced-by-count":76,"title":["Hemozoin Induces Lung Inflammation and Correlates with Malaria-Associated Acute Respiratory Distress Syndrome"],"prefix":"10.1093","volume":"48","author":[{"given":"Katrien","family":"Deroost","sequence":"first","affiliation":[{"name":"Laboratory of Immunobiology, and"}]},{"given":"Ariane","family":"Tyberghein","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, and"}]},{"given":"Natacha","family":"Lays","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, and"}]},{"given":"Sam","family":"Noppen","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, and"}]},{"given":"Evelin","family":"Schwarzer","sequence":"additional","affiliation":[{"name":"Department of Genetics, Biology, and Biochemistry, and"}]},{"given":"Els","family":"Vanstreels","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, and"}]},{"given":"Mina","family":"Komuta","sequence":"additional","affiliation":[{"name":"Translational Cell and Tissue Research, KU Leuven\u2013University of Leuven, Leuven, Belgium"}]},{"given":"Mauro","family":"Prato","sequence":"additional","affiliation":[{"name":"Department of Genetics, Biology, and Biochemistry, and"},{"name":"Department of Neuroscience, University of Turin, Turin, Italy"}]},{"given":"Jing-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; and"}]},{"given":"Ana","family":"Pamplona","sequence":"additional","affiliation":[{"name":"Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Chris J.","family":"Janse","sequence":"additional","affiliation":[{"name":"Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; and"}]},{"given":"Paolo","family":"Arese","sequence":"additional","affiliation":[{"name":"Department of Genetics, Biology, and Biochemistry, and"}]},{"given":"Tania","family":"Roskams","sequence":"additional","affiliation":[{"name":"Translational Cell and Tissue Research, KU Leuven\u2013University of Leuven, Leuven, Belgium"}]},{"given":"Dirk","family":"Daelemans","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, and"}]},{"given":"Ghislain","family":"Opdenakker","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, and"}]},{"given":"Philippe E.","family":"Van den Steen","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, and"}]}],"member":"286","published-online":{"date-parts":[[2013,5,1]]},"reference":[{"key":"2026021904201839900_bib1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4269\/ajtmh.77.6.suppl.29","article-title":"The management of patients with severe malaria","volume":"77","author":"Day","year":"2007","journal-title":"Am J Trop Med Hyg"},{"key":"2026021904201839900_bib2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1146\/annurev-pathol-011110-130158","article-title":"The acute respiratory distress syndrome: pathogenesis and treatment","volume":"6","author":"Matthay","year":"2011","journal-title":"Annu Rev Pathol"},{"key":"2026021904201839900_bib3","first-page":"179","article-title":"Acute lung injury and acute 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