Inherited surfactant protein-B deficiency and surfactant protein-C associated disease: clinical features and evaluation.
ABSTRACT The pulmonary surfactant is a mixture of phospholipids and proteins synthesized, packaged, and secreted by alveolar type II cells that lowers surface tension and prevents atelectasis at end-expiration. A tightly regulated, complex metabolic cycle involves all components of the pulmonary surfactant. Disorders of surfactant metabolism that have a genetic basis are rare, but causes of respiratory dysfunction in infants and children emerge. Recessive loss of function mutations in surfactant protein-B (SP-B) gene lead to respiratory failure that is lethal in the newborn period while single allelic mutations in the surfactant protein-C (SP-C) gene cause interstitial lung disease of varying severity and age of onset. The genetic basis, mechanisms, clinical presentation and outcome, diagnostic approach and limited therapeutic options for disease due to mutations the SP-B and SP-C genes will be described in detail in this article. These disorders provide insights into some of the distinct mechanisms that disrupt the surfactant metabolic cycle and cause respiratory disease in infants and children.
- NeoReviews 10/2008; 9(10).
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ABSTRACT: Surfactant proteins (SP) have been studied intensively in the respiratory system. Surfactant protein A and surfactant protein D are proteins belonging to the family of collectins each playing a major role in the innate immune system. The ability of surfactant protein A and surfactant protein D to bind various pathogens and facilitate their elimination has been described in a vast number of studies. Surfactant proteins are very important in modulating the host's inflammatory response and participate in the clearance of apoptotic cells. Surfactant protein B and surfactant protein C are proteins responsible for lowering the surface tension in the lungs. The aim of this study was an investigation of expression of surfactant proteins in the central nervous system to assess their specific distribution patterns. The second aim was to quantify surfactant proteins in cerebrospinal fluid of healthy subjects compared to patients suffering from different neuropathologies. The expression of mRNA for the surfactant proteins was analyzed with RT-PCR done with samples from different parts of the human brain. The production of the surfactant proteins in the brain was verified using immunohistochemistry and Western blot. The concentrations of the surfactant proteins in cerebrospinal fluid from healthy subjects and patients suffering from neuropathologic conditions were quantified using ELISA. Our results revealed that surfactant proteins are present in the central nervous system and that the concentrations of one or more surfactant proteins in healthy subjects differed significantly from those of patients affected by central autoimmune processes, CNS infections or cerebral infarction. Based on the localization of the surfactant proteins in the brain, their different levels in normal versus pathologic samples of cerebrospinal fluid and their well-known functions in the lungs, it appears that the surfactant proteins may play roles in host defense of the brain, facilitation of cerebrospinal fluid secretion and maintenance of the latter's rheological properties.PLoS ONE 11/2013; 8(9):e74412. · 3.53 Impact Factor
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ABSTRACT: Background:Genetic variations associated with interstitial lung diseases (ILD) have not been extensively studied in Japanese infants.Methods:Forty-three infants with unexplained lung dysfunction were studied. All 43, 22, and 17 infants underwent analyses of surfactant protein (SP)-C gene (SFTPC) and ATP-binding cassette A3 gene (ABCA3), SP-B gene (SFTPB), and SP-B western blotting, respectively. Two and four underwent assessment of GM-CSF stimulating phosphorylation of signal transducer and activator of transcription-5 (pSTAT-5) and analyses of FOXF1 gene (FOXF1), respectively.Results:ILD was diagnosed clinically in nine infants: four, three, and two had interstitial pneumonitis (IP), hereditary pulmonary alveolar proteinosis (hPAP), and alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), respectively. Genetic variations considered responsible were detected in six (67%) of the nine infants with ILD: in three with hPAP (SFTPC p.Leu45Arg and p.Gln145fs, and ABCA3 p.Arg1583Trp/p.Val1495CysfsX21), two with IP (SFTPC p.Lys63Glu and p.Ser72Asn/p.Gly100Ala), and one with ACD/MPV (FOXF1 p.Leu300ArgfsX79). None showed SFTPB mutations or defects in pSTAT-5. The 17 BAL or tracheal aspirates contained exclusively SP-B protein.Conclusion:The SP-C abnormality was most prevalent and SP-B deficiency was rare in Japanese infants with hereditary ILD.Pediatric Research (2014); doi:10.1038/pr.2014.114.Pediatric Research 08/2014; · 2.84 Impact Factor