Surfactant Protein A and D Polymorphisms and Methylprednisolone Pharmacogenetics in Donor Lungs

Abstract Objective 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. Methods 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. Results In NCI-H441 cells, methylprednisolone treatment at 10 −5  M and 10 −6  M reduced surfactant protein A1 and surfactant protein A2 messenger RNA and surfactant protein A protein expression ( P x ) variants: Surfactant protein A1, A2, and D messenger RNA expression were greater for 1A 0 versus 1A 1 ( P 2 6A 2 /1A 0 1A 0 (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 Conclusions 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 0 have a greater expression of surfactant protein A when treated with methylprednisolone. Surfactant protein A polymorphisms could be used to personalize immunosuppressive regimens.