Studies about the serine protease inhibitors rBmTI-A and rBmTI-6 in the pulmonary emphysema inflammatory process.
Pulmonary emphysema is a manifestation of chronic obstructive pulmonary
disease (COPD) and it is characterized by progressive airflow limitation. It
is generally irreversible and the installment of the disease is a consequence
of the destruction of elastin, a component of the elastic fibers of the lung, by
the enzyme elastase. This enzyme is found in secreted granules of neutrophils
and alveolar macrophages, performing the digestion of microorganisms, cell
debris and coagulation products. Its main function is to protect lung tissue.
Some enzymes are related to the pathogenesis of emphysema such as human
neutrophil elastase, kallikreins and metalloproteinases 9 and 12. In previ-
ous studies, the use of Kunitz-BPTI serine protease inhibitors rBmTI-A and
rBmTI-6 resulted in the prevention of pulmonary emphysema, controlling
the common inflammatory response observed in the disease and reducing the
bronchoalveolar lavage proteolytic activity. In this work, three-dimensional
models of the two inhibitors were obtained and their interaction with kalli-
kreins KLK1, KLK5, KLK6, KLK6 and KLK7 were solved through molecular
docking. The results pointed to stable and energetically possible interacti-
ons, highlighting the participation of the amino acid Leu from P1 site of the
second domain of rBmTI-A. Data from cDNA microarray experiment were
analysed to understand the effects of rBmTI-6 inhibitor in animal model of
induced pulmonary emphysema by porcine pancreatic elastase. The results
demonstrated that the pulmonary emphysema was successfully established
in the studied model and the administration of the inhibitor decreased the
inflammatory processes linked to the development of the disease.