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Pulm Pharmacol Ther. 2014 Apr;27(2):144-9. doi: 10.1016/j.pupt.2013.04.003. Epub 2013 Apr 17.

Recovery of pulmonary structure and exercise capacity by treatment with granulocyte-colony stimulating factor (G-CSF) in a mouse model of emphysema.

Author information

1
Programa de Pós-Graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil. Electronic address: gustavofortunato@cirtoraxbahia.com.br.
2
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, BA, Brazil. Electronic address: andion07@hotmail.com.
3
Departamento de Biologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, SP, Brazil; Instituto Nacional de Ciência e Tecnologia em Fisiologia Comparada, UNESP, Rio Claro, SP, Brazil. Electronic address: klein@ffclrp.usp.br.
4
Programa de Pós-Graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, BA, Brazil. Electronic address: assbneto@hotmail.com.
5
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil. Electronic address: anangrisani@hotmail.com.
6
Programa de Pós-Graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil; Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil. Electronic address: julianafvs@gmail.com.
7
Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, BA, Brazil. Electronic address: carlakaneto@gmail.com.
8
Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, BA, Brazil. Electronic address: brunosolanosouza@gmail.com.
9
Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, BA, Brazil. Electronic address: ricardo.ribeiro@hsr.com.br.
10
Programa de Pós-Graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil; Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, BA, Brazil. Electronic address: milena@bahia.fiocruz.br.
11
Programa de Pós-Graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil; Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, BA, Brazil; Departamento de Biofunção, Instituto de Ciências da Saúde, Universidade Federal da Bahia, BA, Brazil. Electronic address: simone@bahia.fiocruz.br.

Abstract

Emphysema is a chronic obstructive pulmonary disease characterized abnormal dilatation of alveolar spaces, which impairs alveolar gas exchange, compromising the physical capacity of a patient due to airflow limitations. Here we tested the effects of G-CSF administration in pulmonary tissue and exercise capacity in emphysematous mice. C57Bl/6 female mice were treated with elastase intratracheally to induce emphysema. Their exercise capacities were evaluated in a treadmill. Lung histological sections were prepared to evaluate mean linear intercept measurement. Emphysematous mice were treated with G-CSF (3 cycles of 200 μg/kg/day for 5 consecutive days, with 7-day intervals) or saline and submitted to a third evaluation 8 weeks after treatment. Values of run distance and linear intercept measurement were expressed as mean ± SD and compared applying a paired t-test. Effects of treatment on these parameters were analyzed applying a Repeated Measures ANOVA, followed by Tukey's post hoc analysis. p < 0.05 was considered statistically significant. Twenty eight days later, animals ran significantly less in a treadmill compared to normal mice (549.7 ± 181.2 m and 821.7 ± 131.3 m, respectively; p < 0.01). Treatment with G-CSF significantly increased the exercise capacity of emphysematous mice (719.6 ± 200.5 m), whereas saline treatment had no effect on distance run (595.8 ± 178.5 m). The PCR cytokines genes analysis did not detect difference between experimental groups. Morphometric analyses in the lung showed that saline-treated mice had a mean linear intercept significantly higher (p < 0.01) when compared to mice treated with G-CSF, which did not significantly differ from that of normal mice. Treatment with G-CSF promoted the recovery of exercise capacity and regeneration of alveolar structural alterations in emphysematous mice.

KEYWORDS:

Exercise capacity; G-CSF; Mean linear intercept; Pulmonary emphysema

PMID:
23603459
DOI:
10.1016/j.pupt.2013.04.003
[Indexed for MEDLINE]

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