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 < .05). A pharmacogenetic relationship was observed in human donor precision-cut lung slices between the surfactant protein A2 (1Ax) 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).

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 1A0 have a greater expression of surfactant protein A when treated with methylprednisolone. Surfactant protein A polymorphisms could be used to personalize immunosuppressive regimens.

• Authors: Beatrice Aramini, Patrick Geraghty, David J Lederer, Joseph Costa, Susan L DiAngelo, Joanna Floros, Frank D'Ovidio
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 157 Issue 5 Pg. 2109-2117 (05 2019) ISSN: 1097-685X [Electronic] United States
• PMID: 30827536 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Chemical References

• Glucocorticoids
• Immunosuppressive Agents
• Pulmonary Surfactant-Associated Protein A
• Pulmonary Surfactant-Associated Protein D
• SFTPA1 protein, human
• SFTPA2 protein, human
• Methylprednisolone

Topics

• Cell Line
• Dose-Response Relationship, Drug
• Gene Expression Regulation
• Gene Frequency
• Genotype
• Glucocorticoids (pharmacology)
• Humans
• Immunosuppressive Agents (pharmacology)
• In Vitro Techniques
• Lung (drug effects, metabolism)
• Lung Transplantation
• Methylprednisolone (pharmacology)
• Pharmacogenomic Variants
• Polymorphism, Genetic
• Pulmonary Surfactant-Associated Protein A (genetics, metabolism)
• Pulmonary Surfactant-Associated Protein D (genetics, metabolism)
• Tissue Donors