{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:31:03Z","timestamp":1789655463960,"version":"4.0.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"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":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Pulmonary alveolar proteinosis (PAP) is characterized by filling of the alveolar spaces by lipoprotein-rich material of ill-defined composition, and is caused by molecularly different and often rare diseases that occur from birth to old age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To perform a quantitative lipidomic analysis of lipids and the surfactant proteins A, B, and C in lavage fluids from patients with proteinosis of different causes in comparison with healthy control subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>During the last two decades, we have collected BAL samples from patients with PAP due to autoantibodies against granulocyte\u2013macrophage colony\u2013stimulating factor; genetic mutations in CSF2RA (colony-stimulating factor 2 receptor \u03b1-subunit), MARS (methionyl aminoacyl-tRNA synthetase), FARSB (phenylalanine-tRNA synthetase, \u03b2-subunit), and NPC2 (Niemann-Pick disease type C2); and secondary to myeloid leukemia. Their lipid composition was quantified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Free cholesterol was largely increased by 60-fold and cholesteryl esters were increased by 24-fold. There was an excessive, more than 130-fold increase in ceramide and other sphingolipids. In particular, the long-chain ceramides d18:1\/20:0 and d18:1\/24:0 were elevated and likely contributed to the proapoptotic environment observed in PAP. Cellular debris lipids such as phosphatidylethanolamine and phosphatidylserine were only moderately increased, by four- to sevenfold. The surfactant lipid class phosphatidylcholine expanded 17-fold, lysophosphatidylcholine expanded 54-fold, and the surfactant proteins A, B, and C expanded 144-, 4-, and 17-fold, respectively. These changes did not differ among the various diseases that cause PAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This insight into the alveolar lipidome may provide monitoring tools and lead to new therapeutic strategies for PAP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201901-0086oc","type":"journal-article","created":{"date-parts":[[2019,4,19]],"date-time":"2019-04-19T14:06:22Z","timestamp":1555682782000},"page":"881-887","source":"Crossref","is-referenced-by-count":35,"title":["Quantitative Lipidomics in Pulmonary Alveolar Proteinosis"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0113-912X","authenticated-orcid":false,"given":"Matthias","family":"Griese","sequence":"first","affiliation":[{"name":"German Center for Lung Research, Dr. von Hauner Children\u2019s Hospital, Ludwig Maximilians University, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bonella","sequence":"additional","affiliation":[{"name":"Center for Interstitial and Rare Lung Diseases, Department of Pneumology, Ruhrlandklinik University Hospital, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Costabel","sequence":"additional","affiliation":[{"name":"Center for Interstitial and Rare Lung Diseases, Department of Pneumology, Ruhrlandklinik University Hospital, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"de Blic","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker-Enfants Malades, Paris, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen-Binh","family":"Tran","sequence":"additional","affiliation":[{"name":"German Center for Lung Research, Dr. von Hauner Children\u2019s Hospital, Ludwig Maximilians University, 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