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Surfactant protein A and D polymorphisms and methylprednisolone pharmacogenetics in donor lungs.
- Source :
- Journal of Thoracic & Cardiovascular Surgery; May2019, Vol. 157 Issue 5, p2109-2117, 9p
- Publication Year :
- 2019
-
Abstract
- Surfactant proteins A and D are important molecules involved in lung allograft innate immunity. Genetic polymorphisms of surfactant proteins A and D are associated with various lung diseases. In this study, surfactant protein A and D expression responses were investigated during pharmacogenetics upon methylprednisolone treatment as observed during lung transplantation. A human cell line (NCI-H441) and precision-cut lung slices from 16 human donors were incubated with methylprednisolone, and surfactant protein A1, surfactant protein A2, and surfactant protein D messenger RNA and surfactant protein A protein expression were assayed. Surfactant protein A1, A2, and D polymorphisms and surfactant protein A gene and protein expressions were determined. In NCI-H441 cells, methylprednisolone treatment at 10<superscript>−5</superscript> M and 10<superscript>−6</superscript> M reduced surfactant protein A1 and surfactant protein A2 messenger RNA and surfactant protein A protein expression (P <.05). A pharmacogenetic relationship was observed in human donor precision-cut lung slices between the surfactant protein A2 (1A<superscript>x</superscript>) variants: Surfactant protein A1, A2, and D messenger RNA expression were greater for 1A<superscript>0</superscript> versus 1A<superscript>1</superscript> (P <.05); surfactant protein A1/surfactant protein A2 genotype 6A<superscript>2</superscript>6A<superscript>2</superscript>/1A<superscript>0</superscript>1A<superscript>0</superscript> (n = 5) showed greater surfactant protein A1, A2, and D messenger RNA expression and surfactant protein A protein expression compared with the other surfactant protein A1/surfactant protein A2 genotypes (n = 11) (P <.05). The surfactant protein A genotype and methylprednisolone stimuli influence donor lung surfactant protein A and D expression. Lungs carrying the surfactant protein A2 variant 1A<superscript>0</superscript> have a greater expression of surfactant protein A when treated with methylprednisolone. Surfactant protein A polymorphisms could be used to personalize immunosuppressive regimens. The pharmacogenetic relationship between SP-A polymorphic variants and methylprednisolone was studied in PCLS obtained from 16 human donor lungs. The SP-A1 and SP-A2 genotypes were determined by applying, in a blinded fashion, a pyrosequencing protocol, and PCLS were treated with methylprednisolone. The SP-A1 and SP-A2 mRNA expression and SP-A protein expression were assayed relative to the control untreated PCLS showing a greater expression in lungs from donors with SP-A1/SP-A2 genotype 6A<superscript>2</superscript>6A<superscript>2</superscript>/1A<superscript>0</superscript>1A<superscript>0</superscript>. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00225223
- Volume :
- 157
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Journal of Thoracic & Cardiovascular Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 136343140
- Full Text :
- https://doi.org/10.1016/j.jtcvs.2018.12.098