Reduced proteolysis of surfactant protein A and changes of the bronchoalveolar lavage fluid proteome by inhaled alpha 1-protease inhibitor in cystic fibrosis.

In cystic fibrosis (CF), the chronic neutrophilic inflammation of the airways results in proteolytic degradation of lung tissue early in the course of the disease. Inhalation of alpha 1-protease inhibitor (alpha 1-PI) may restore the protease-antiprotease imbalance and thus lead to less tissue damage. To monitor its impacts on bronchoalveolar lavage (BAL) fluid protein pattern (proteome) and on surfactant protein A (SP-A), eight young adults with CF inhaled 100 mg of alpha 1-PI twice daily over eight weeks. BAL fluids were obtained before and after inhalation. Total protein, the number and amount of proteins with a molecular mass < 20 kDa were reduced compared to pretreatment values. Degradation products of SP-A were shown by immunoblotting, being reduced after alpha 1-PI treatment. This pilot study demonstrates that inhalation of alpha 1-PI is associated with biochemical changes consistent with reduced proteolysis. The display of the BAL proteome by two-dimensional electrophoresis may be helpful to quantify the overall molecular changes associated with proteolytic or other lung injuries and offers the possibility to monitor directly therapeutic interventions.