title: A treatment with a protease inhibitor recombinant from the cattle tick (Rhipicephalus Boophilus microplus) ameliorates emphysema in mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Juliana D
authors.initials: JD
authors.lastname: Lourenço
authors.affiliation: Centro de Ciências Naturais e Humanas, UFABC, Santo André, Sao Paulo, Brazil.
authors.forename: Luana P
authors.initials: LP
authors.lastname: Neves
authors.affiliation: Department of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Clarice R
authors.initials: CR
authors.lastname: Olivo
authors.affiliation: Centro de Ciências Naturais e Humanas, UFABC, Santo André, Sao Paulo, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Duran
authors.affiliation: Department of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Francine M
authors.initials: FM
authors.lastname: Almeida
authors.affiliation: Department of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Petra M M
authors.initials: PM
authors.lastname: Arantes
authors.affiliation: Biological Science Department, UNIFESP, Sao Paulo, Brazil.
authors.forename: Carla M
authors.initials: CM
authors.lastname: Prado
authors.affiliation: Department of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Edna Aparecida
authors.initials: EA
authors.lastname: Leick
authors.affiliation: Departamento de Bioquímica, UNIFESP-EPM, Sao Paulo, Brazil.
authors.forename: Aparecida S
authors.initials: AS
authors.lastname: Tanaka
authors.affiliation: Department of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Mílton A
authors.initials: MA
authors.lastname: Martins
authors.affiliation: Centro de Ciências Naturais e Humanas, UFABC, Santo André, Sao Paulo, Brazil.
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Sasaki
authors.affiliation: Department of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Fernanda D T Q S
authors.initials: FD
authors.lastname: Lopes
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002417:Cattle; D003094:Collagen / Q000378:metabolism; D004548:Elasticity / Q000187:drug effects; D037502:Galectin 3 / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011656:Pulmonary Emphysema / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000627:therapeutic use*; D015656:Respiratory Mechanics / Q000187:drug effects; D048494:Rhipicephalus / Q000378:metabolism*
chemical_list: D037502:Galectin 3; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D003094:Collagen; D053508:Matrix Metalloproteinase 12