Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA Mouse
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
Affiliations
Tamara L. Paget
Mechanisms in Cell Biology and Disease Group, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia
Emma J. Parkinson-Lawrence
Mechanisms in Cell Biology and Disease Group, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia
Paul J. Trim
Proteomics, Metabolomics and MS-Imaging Core Facility, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
Chiara Autilio
Department of Biochemistry, Faculty of Biology and Research Institute Hospital 12 de Octubre (Imas12), Complutense University, 28003 Madrid, Spain
Madhuriben H. Panchal
Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
Grielof Koster
Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
Mercedes Echaide
Department of Biochemistry, Faculty of Biology and Research Institute Hospital 12 de Octubre (Imas12), Complutense University, 28003 Madrid, Spain
Marten F. Snel
Proteomics, Metabolomics and MS-Imaging Core Facility, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
Anthony D. Postle
Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
Janna L. Morrison
Early Origins Adult Health Research Group, Health and Biomedical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia
Jésus Pérez-Gil
Department of Biochemistry, Faculty of Biology and Research Institute Hospital 12 de Octubre (Imas12), Complutense University, 28003 Madrid, Spain
Sandra Orgeig
Mechanisms in Cell Biology and Disease Group, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia
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.