The Effect of Immunosuppression on Airway Integrity.

Abstract:

BACKGROUND:Insults to the airway epithelium play a key role in constrictive bronchiolitis after lung transplantation, the typical hallmark of chronic rejection. Our hypothesis is that immunosuppressives might affect airway integrity. METHODS:A biculture of human bronchial epithelial cells and lung microvascular endothelial cells was exposed to immunosuppressives (serum through levels) for 24 hours or 4 days. Cytotoxicity, transepithelial electrical resistance (TEER), and permeability was measured after exposure to monotherapies and combination therapies. Apoptosis, oxidative stress, inflammation (IL-8), real-time polymerase chain reaction for epithelial-to-mesenchymal transition and tight junction proteins were assessed in exposed cells. RESULTS:Mycophenolate mofetil (MMF) and combination therapies including MMF, at serum trough levels and higher, are toxic for the human bronchial epithelial cells after 4-day exposure. Moreover, already after 24 hours, TEER of cells exposed to MMF decreases and permeability increases. MMF did not induce apoptosis, oxidative stress, loss of tight junctions or production of IL-8 after 24 hours, but possibly induces epithelial-to-mesenchymal transition in epithelial cells. MMF was detectable at both sides of the biculture and was also present in bronchoalveolar lavage of lung transplantation patients. Other immunosuppressives were not toxic, neither changed TEER or permeability. CONCLUSIONS:Our findings suggest that MMF is present in the airways of lung transplant patients and might affect the structural integrity of the airway, which needs further investigation and validation in the clinical setting.

journal_name

Transplantation

journal_title

Transplantation

authors

Bellon H,Vandermeulen E,Verleden SE,Heigl T,Vriens H,Lammertyn E,Verlinden L,Vanhove T,Verstuyf M,Hoet P,Vos R,Verleden GM,Vanaudenaerde BM

doi

10.1097/TP.0000000000001809

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

2855-2861

issue

12

eissn

0041-1337

issn

1534-6080

journal_volume

101

pub_type

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