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A Pilot Study to Examine the Effect of Chronic Treatment with Immunosuppressive Drugs on Mucociliary Clearance in a Vagotomized Murine Model

BACKGROUND: Previously, we have demonstrated that mucociliary clearance (MCC) is diminished within the first months after surgery in lung transplant patients and the explanation for the reduction in MCC is unknown. We hypothesized that chronic treatment with a commonly prescribed regimen of immunosu...

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Autores principales: Bhashyam, Abhiram R., Mogayzel, Peter J., McGrath-Morrow, Sharon, Neptune, Enid, Malinina, Alla, Fox, James, Laube, Beth L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447941/
https://www.ncbi.nlm.nih.gov/pubmed/23028925
http://dx.doi.org/10.1371/journal.pone.0045312
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author Bhashyam, Abhiram R.
Mogayzel, Peter J.
McGrath-Morrow, Sharon
Neptune, Enid
Malinina, Alla
Fox, James
Laube, Beth L.
author_facet Bhashyam, Abhiram R.
Mogayzel, Peter J.
McGrath-Morrow, Sharon
Neptune, Enid
Malinina, Alla
Fox, James
Laube, Beth L.
author_sort Bhashyam, Abhiram R.
collection PubMed
description BACKGROUND: Previously, we have demonstrated that mucociliary clearance (MCC) is diminished within the first months after surgery in lung transplant patients and the explanation for the reduction in MCC is unknown. We hypothesized that chronic treatment with a commonly prescribed regimen of immunosuppressive drugs significantly impairs MCC. We tested this hypothesis in a murine model of lung transplantation. METHODS: Fifteen C57BL/6 mice underwent vagotomy on the right side to simulate denervation associated with lung transplantation in humans. For 6 days, seven mice (controls) were intraperitoneally injected with three 100 µL doses of phosphate buffered saline and eight mice (immunosuppressed) were injected with three 100 µL injections of tacrolimus (1 mg/kg), mycophenolate mofetil (30 mg/kg), and prednisone (2 mg/kg) once daily. Then, mice inhaled the radioisotope (99m)technetium and underwent gamma camera imaging of their lungs for 6.5 hrs. Counts in the right lung at 1–1.5 hrs and at 6–6.5 hrs were first background-corrected and then decay-corrected to time 0 counts. Decay-corrected counts were then divided by time 0 counts. Retention at each time point was subtracted from 1.00 and multiplied by 100% to obtain percent removed by mucociliary clearance. RESULTS: Although there was a slowing of MCC at 1–1.5 hrs for the immunosuppressed mice, there was no statistical difference in MCC measured at 1–1.5 hrs for the two groups of mice. At 6–6.5 hrs, MCC was significantly slower in the immunosuppressed mice, compared to controls, with 7.78±5.9% cleared versus 23.01±11.7% cleared, respectively (p = 0.006). CONCLUSIONS: These preliminary results suggest that chronic treatment with immunosuppressive medications significantly slows MCC in vagotomized C57BL/6 mice. These findings could shed light on why MCC is reduced in lung transplant patients whose lungs are denervated during surgery and who are chronically treated with immunosuppressive drugs post surgery.
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spelling pubmed-34479412012-10-01 A Pilot Study to Examine the Effect of Chronic Treatment with Immunosuppressive Drugs on Mucociliary Clearance in a Vagotomized Murine Model Bhashyam, Abhiram R. Mogayzel, Peter J. McGrath-Morrow, Sharon Neptune, Enid Malinina, Alla Fox, James Laube, Beth L. PLoS One Research Article BACKGROUND: Previously, we have demonstrated that mucociliary clearance (MCC) is diminished within the first months after surgery in lung transplant patients and the explanation for the reduction in MCC is unknown. We hypothesized that chronic treatment with a commonly prescribed regimen of immunosuppressive drugs significantly impairs MCC. We tested this hypothesis in a murine model of lung transplantation. METHODS: Fifteen C57BL/6 mice underwent vagotomy on the right side to simulate denervation associated with lung transplantation in humans. For 6 days, seven mice (controls) were intraperitoneally injected with three 100 µL doses of phosphate buffered saline and eight mice (immunosuppressed) were injected with three 100 µL injections of tacrolimus (1 mg/kg), mycophenolate mofetil (30 mg/kg), and prednisone (2 mg/kg) once daily. Then, mice inhaled the radioisotope (99m)technetium and underwent gamma camera imaging of their lungs for 6.5 hrs. Counts in the right lung at 1–1.5 hrs and at 6–6.5 hrs were first background-corrected and then decay-corrected to time 0 counts. Decay-corrected counts were then divided by time 0 counts. Retention at each time point was subtracted from 1.00 and multiplied by 100% to obtain percent removed by mucociliary clearance. RESULTS: Although there was a slowing of MCC at 1–1.5 hrs for the immunosuppressed mice, there was no statistical difference in MCC measured at 1–1.5 hrs for the two groups of mice. At 6–6.5 hrs, MCC was significantly slower in the immunosuppressed mice, compared to controls, with 7.78±5.9% cleared versus 23.01±11.7% cleared, respectively (p = 0.006). CONCLUSIONS: These preliminary results suggest that chronic treatment with immunosuppressive medications significantly slows MCC in vagotomized C57BL/6 mice. These findings could shed light on why MCC is reduced in lung transplant patients whose lungs are denervated during surgery and who are chronically treated with immunosuppressive drugs post surgery. Public Library of Science 2012-09-20 /pmc/articles/PMC3447941/ /pubmed/23028925 http://dx.doi.org/10.1371/journal.pone.0045312 Text en © 2012 Bhashyam et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bhashyam, Abhiram R.
Mogayzel, Peter J.
McGrath-Morrow, Sharon
Neptune, Enid
Malinina, Alla
Fox, James
Laube, Beth L.
A Pilot Study to Examine the Effect of Chronic Treatment with Immunosuppressive Drugs on Mucociliary Clearance in a Vagotomized Murine Model
title A Pilot Study to Examine the Effect of Chronic Treatment with Immunosuppressive Drugs on Mucociliary Clearance in a Vagotomized Murine Model
title_full A Pilot Study to Examine the Effect of Chronic Treatment with Immunosuppressive Drugs on Mucociliary Clearance in a Vagotomized Murine Model
title_fullStr A Pilot Study to Examine the Effect of Chronic Treatment with Immunosuppressive Drugs on Mucociliary Clearance in a Vagotomized Murine Model
title_full_unstemmed A Pilot Study to Examine the Effect of Chronic Treatment with Immunosuppressive Drugs on Mucociliary Clearance in a Vagotomized Murine Model
title_short A Pilot Study to Examine the Effect of Chronic Treatment with Immunosuppressive Drugs on Mucociliary Clearance in a Vagotomized Murine Model
title_sort pilot study to examine the effect of chronic treatment with immunosuppressive drugs on mucociliary clearance in a vagotomized murine model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447941/
https://www.ncbi.nlm.nih.gov/pubmed/23028925
http://dx.doi.org/10.1371/journal.pone.0045312
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