A Treatment with a Protease Inhibitor Recombinant from the Cattle Tick (Rhipicephalus Boophilus microplus) Ameliorates Emphysema in Mice

A Treatment with a Protease Inhibitor Recombinant from the Cattle Tick (Rhipicephalus Boophilus microplus) Ameliorates Emphysema in Mice

Author Lourenco, Juliana D. Google Scholar
Neves, Luana P. Google Scholar
Olivo, Clarice R. Google Scholar
Duran, Adriana Google Scholar
Almeida, Francine M. Google Scholar
Arantes, Petra M. M. Google Scholar
Prado, Carla M. Autor UNIFESP Google Scholar
Leick, Edna Aparecida Google Scholar
Tanaka, Aparecida S. Autor UNIFESP Google Scholar
Martins, Milton A. Google Scholar
Sasaki, Sergio D. Google Scholar
Lopes, Fernanda D. T. Q. S. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do ABC (UFABC)
Abstract Aims: To determine whether a serine protease inhibitor treatment can prevent or minimize emphysema in mice.Methods: C57BL/6 mice were subjected to porcine pancreatic elastase (PPE) nasal instillation to induce emphysema and were treated with a serine protease inhibitor (rBmTI-A) before (Protocol 1) and after (Protocol 2) emphysema development. in both protocols, we evaluated lung function to evaluate the airway resistance (Raw), tissue damping (Gtis) and tissue elastance (Htis). the inflammatory profile was analyzed in the bronchoalveolar lavage (BALF) and through the use of morphometry; we measured the mean linear intercept (Lm) (to verify alveolar enlargement), the volume proportion of collagen and elastic fibers, and the numbers of macrophages and metalloprotease 12 (MMP-12) positive cells in the parenchyma. We showed that at both time points, even after the emphysema was established, the rBmTI-A treatment was sufficient to reverse the loss of elastic recoil measured by Htis, the alveolar enlargement and the increase in the total number of cells in the BALF, with a primary decrease in the number of macrophages. Although, the treatment did not control the increase in macrophages in the lung parenchyma, it was sufficient to decrease the number of positive cells for MMP-12 and reduce the volume of collagen fibers, which was increased in PPE groups. These findings attest to the importance of MMP-12 in PPE-induced emphysema and suggest that this metalloprotease could be an effective therapeutic target.
Language English
Sponsor Laboratorios de Investigacao Medica do Hospital das Clinicas da Faculdade de Medicina da USP (LIM/HC)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Date 2014-06-02
Published in Plos One. San Francisco: Public Library Science, v. 9, n. 6, 9 p., 2014.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 9
Origin http://dx.doi.org/10.1371/journal.pone.0098216
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000336956300048
URI http://repositorio.unifesp.br/handle/11600/37854

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