Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA Mouse
Mucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disease with significant neurological and skeletal pathologies. Respiratory dysfunction is a secondary pathology contributing to mortality in MPS IIIA patients. Pulmonary surfactant is crucial to optimal lung function and has not been inve...
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MDPI AG
2021-04-01
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| author | Tamara L. Paget Emma J. Parkinson-Lawrence Paul J. Trim Chiara Autilio Madhuriben H. Panchal Grielof Koster Mercedes Echaide Marten F. Snel Anthony D. Postle Janna L. Morrison Jésus Pérez-Gil Sandra Orgeig |
| author_facet | Tamara L. Paget Emma J. Parkinson-Lawrence Paul J. Trim Chiara Autilio Madhuriben H. Panchal Grielof Koster Mercedes Echaide Marten F. Snel Anthony D. Postle Janna L. Morrison Jésus Pérez-Gil Sandra Orgeig |
| author_sort | Tamara L. Paget |
| collection | DOAJ |
| description | Mucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disease with significant neurological and skeletal pathologies. Respiratory dysfunction is a secondary pathology contributing to mortality in MPS IIIA patients. Pulmonary surfactant is crucial to optimal lung function and has not been investigated in MPS IIIA. We measured heparan sulphate (HS), lipids and surfactant proteins (SP) in pulmonary tissue and bronchoalveolar lavage fluid (BALF), and surfactant activity in healthy and diseased mice (20 weeks of age). Heparan sulphate, ganglioside GM3 and bis(monoacylglycero)phosphate (BMP) were increased in MPS IIIA lung tissue. There was an increase in HS and a decrease in BMP and cholesteryl esters (CE) in MPS IIIA BALF. Phospholipid composition remained unchanged, but BALF total phospholipids were reduced (49.70%) in MPS IIIA. There was a reduction in SP-A, -C and -D mRNA, SP-D protein in tissue and SP-A, -C and -D protein in BALF of MPS IIIA mice. Captive bubble surfactometry showed an increase in minimum and maximum surface tension and percent surface area compression, as well as a higher compressibility and hysteresis in MPS IIIA surfactant upon dynamic cycling. Collectively these biochemical and biophysical changes in alveolar surfactant are likely to be detrimental to lung function in MPS IIIA. |
| first_indexed | 2024-03-10T12:28:46Z |
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| id | doaj.art-303771f4fc134b0c98d59b93b6277ab1 |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:28:46Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-303771f4fc134b0c98d59b93b6277ab12023-11-21T14:46:37ZengMDPI AGCells2073-44092021-04-0110484910.3390/cells10040849Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA MouseTamara L. Paget0Emma J. Parkinson-Lawrence1Paul J. Trim2Chiara Autilio3Madhuriben H. Panchal4Grielof Koster5Mercedes Echaide6Marten F. Snel7Anthony D. Postle8Janna L. Morrison9Jésus Pérez-Gil10Sandra Orgeig11Mechanisms in Cell Biology and Disease Group, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaMechanisms in Cell Biology and Disease Group, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaProteomics, Metabolomics and MS-Imaging Core Facility, South Australian Health and Medical Research Institute, Adelaide, SA 5000, AustraliaDepartment of Biochemistry, Faculty of Biology and Research Institute Hospital 12 de Octubre (Imas12), Complutense University, 28003 Madrid, SpainFaculty of Medicine, University of Southampton, Southampton SO16 6YD, UKFaculty of Medicine, University of Southampton, Southampton SO16 6YD, UKDepartment of Biochemistry, Faculty of Biology and Research Institute Hospital 12 de Octubre (Imas12), Complutense University, 28003 Madrid, SpainProteomics, Metabolomics and MS-Imaging Core Facility, South Australian Health and Medical Research Institute, Adelaide, SA 5000, AustraliaFaculty of Medicine, University of Southampton, Southampton SO16 6YD, UKEarly Origins Adult Health Research Group, Health and Biomedical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaDepartment of Biochemistry, Faculty of Biology and Research Institute Hospital 12 de Octubre (Imas12), Complutense University, 28003 Madrid, SpainMechanisms in Cell Biology and Disease Group, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaMucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disease with significant neurological and skeletal pathologies. Respiratory dysfunction is a secondary pathology contributing to mortality in MPS IIIA patients. Pulmonary surfactant is crucial to optimal lung function and has not been investigated in MPS IIIA. We measured heparan sulphate (HS), lipids and surfactant proteins (SP) in pulmonary tissue and bronchoalveolar lavage fluid (BALF), and surfactant activity in healthy and diseased mice (20 weeks of age). Heparan sulphate, ganglioside GM3 and bis(monoacylglycero)phosphate (BMP) were increased in MPS IIIA lung tissue. There was an increase in HS and a decrease in BMP and cholesteryl esters (CE) in MPS IIIA BALF. Phospholipid composition remained unchanged, but BALF total phospholipids were reduced (49.70%) in MPS IIIA. There was a reduction in SP-A, -C and -D mRNA, SP-D protein in tissue and SP-A, -C and -D protein in BALF of MPS IIIA mice. Captive bubble surfactometry showed an increase in minimum and maximum surface tension and percent surface area compression, as well as a higher compressibility and hysteresis in MPS IIIA surfactant upon dynamic cycling. Collectively these biochemical and biophysical changes in alveolar surfactant are likely to be detrimental to lung function in MPS IIIA.https://www.mdpi.com/2073-4409/10/4/849MPS IIIASanfilippo syndromepulmonary surfactantrespiratory dysfunctionheparan sulphatebronchoalveolar lavage |
| spellingShingle | Tamara L. Paget Emma J. Parkinson-Lawrence Paul J. Trim Chiara Autilio Madhuriben H. Panchal Grielof Koster Mercedes Echaide Marten F. Snel Anthony D. Postle Janna L. Morrison Jésus Pérez-Gil Sandra Orgeig Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA Mouse Cells MPS IIIA Sanfilippo syndrome pulmonary surfactant respiratory dysfunction heparan sulphate bronchoalveolar lavage |
| title | Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA Mouse |
| title_full | Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA Mouse |
| title_fullStr | Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA Mouse |
| title_full_unstemmed | Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA Mouse |
| title_short | Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA Mouse |
| title_sort | increased alveolar heparan sulphate and reduced pulmonary surfactant amount and function in the mucopolysaccharidosis iiia mouse |
| topic | MPS IIIA Sanfilippo syndrome pulmonary surfactant respiratory dysfunction heparan sulphate bronchoalveolar lavage |
| url | https://www.mdpi.com/2073-4409/10/4/849 |
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