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

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^-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 1A⁰ versus 1A¹ (P < .05); surfactant protein A1/surfactant protein A2 genotype 6A²6A²/1A⁰1A⁰ (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 1A⁰ have a greater expression of surfactant protein A when treated with methylprednisolone. Surfactant protein A polymorphisms could be used to personalize immunosuppressive regimens.