Griese, Matthias and Bonella, Francesco and Costabel, Ulrich and de Blic, Jacques and Nguyen-Binh Tran, and Liebisch, Gerhard (2019) Quantitative Lipidomics in Pulmonary Alveolar Proteinosis. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 200 (7). pp. 881-887. ISSN 1073-449X, 1535-4970
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Rationale: 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. Objectives: 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. Methods: During the last two decades, we have collected BAL samples from patients with PAP due to autoantibodies against granulocyte-macrophage colony-stimulating factor; genetic mutations in CSF2RA (colony-stimulating factor 2 receptor alpha-subunit), MARS (methionyl aminoacyl-tRNA synthetase), FARSB (phenylalanine-tRNA synthetase, (beta-subunit), and NPC2 (Niemann-Pick disease type C2); and secondary to myeloid leukemia. Their lipid composition was quantified. Measurements and Main Results: 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. Conclusions: This insight into the alveolar lipidome may provide monitoring tools and lead to new therapeutic strategies for PAP.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TANDEM MASS-SPECTROMETRY; BRONCHOALVEOLAR LAVAGE FLUID; HIGH-THROUGHPUT QUANTIFICATION; SURFACTANT PROTEINS; CHOLESTERYL ESTER; LUNG-DISEASE; PHOSPHOLIPIDS; EXTRACTION; MUTATIONS; CHILDREN; lipids; pulmonary alveolar proteinosis; BAL |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Mar 2020 13:03 |
| Last Modified: | 26 Mar 2020 13:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26151 |
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