Related Experiment Video
Updated: Jul 6, 2025
In vivo Evaluation of Mucociliary Clearance in Mice
Published on: December 18, 2020
Tacrolimus impairs airway mucociliary clearance of rats
Maristela Prado E Silva1, Sônia de Fátima Soto1, Francine Maria de Almeida2
1Laboratorio de Pesquisa em Cirurgia Toracica, Departamento de Cardiopneumologia, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Insights
Tacrolimus (TAC) impairs airway mucociliary clearance in rats by reducing ciliary beat frequency and mucociliary transport velocity. This immunosuppressive drug also increases acid mucus production, potentially affecting lung transplant recipients.
Area of Science:
- Immunology
- Pulmonology
- Pharmacology
Background:
- Tacrolimus (TAC) is a vital immunosuppressant post-lung transplant.
- TAC's mechanism involves FKBP12 binding, potentially affecting intracellular calcium.
- Ciliary beat frequency (CBF) is calcium-dependent and crucial for airway clearance.
Purpose of the Study:
- To investigate the effect of TAC on airway mucociliary clearance in a rat model.
- To determine if TAC impacts ciliary function and mucus production.
Main Methods:
- Sixty rats were administered either water (control) or TAC for 7, 15, or 30 days.
- Evaluated parameters included mucus transportability, CBF, mucociliary transport velocity (MCTV), and mucus production (acid and neutral).
Main Results:
- TAC significantly decreased CBF and MCTV across all treatment durations.
- Acidic mucus production was significantly increased in TAC-treated rats compared to controls.
- No significant changes were noted in mucus transportability.
Conclusions:
- Tacrolimus impairs airway mucociliary clearance in rats.
- TAC negatively affects ciliary function and alters mucus composition, highlighting potential risks for lung transplant patients.
Objectives:
Tacrolimus (TAC) is the most widely used immunosuppressive agent after lung transplantation. Considering that the ciliary beat frequency (CBF) mainly depends on the cytoplasmic calcium concentration and that TAC can affect this due to its binding with the intracellular immunophilin FKBP12, we hypothesized that TAC could also impair the airway mucociliary clearance of rats.
Methods:
Sixty rats were divided into two groups (n = 30 each): Control = water; TAC = tacrolimus. After 7, 15 or 30 days of treatment, ten animals from each group were euthanized and the following parameters were studied: mucus transportability, CBF, mucociliary transport velocity (MCTV), and neutral and acid mucus production.
Results:
There was a significant decrease in CBF (Control vs TAC: 7 days, p = 0.008; 15 days, p = 0.007; 30 days, p = 0.001) and MCTV (Control vs TAC: 7 days, p = 0.004; 15 days, p < 0.001; 30 days, p < 0.001) in all immunosuppressed animals. TAC therapy also caused an increase in acid mucus production at all treatment times (Control vs TAC: 7 days, p = 0.001; 15 days, p = 0.043; 30 days, p = 0.001).
Conclusions:
TAC impairs airway mucociliary clearance of rats.
