Surfactant protein A and D polymorphisms and methylprednisolone pharmacogenetics in donor lungs

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 < .05). A pharmacogenetic relationship was observed in human donor precision-cut lung slices between the surfactant protein A2 (1A(x)) variants: Surfactant protein A1, A2, and D messenger RNA expression were greater for 1A(0) versus 1A(1) (P < .05); surfactant protein A1/surfactant protein A2 genotype 6A(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 < .05). 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.