title: Reduced proteolysis of surfactant protein A and changes of the bronchoalveolar lavage fluid proteome by inhaled alpha 1-protease inhibitor in cystic fibrosis.
abstract: 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.
authors.affiliation: Childrens' Hospital, Ludwig-Maximilians-University, Munich, Germany. griese@pk-i.med.uni-muenchen.de
authors.forename: M
authors.initials: M
authors.lastname: Griese
authors.forename: C
authors.initials: C
authors.lastname: von Bredow
authors.forename: P
authors.initials: P
authors.lastname: Birrer
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D001992:Bronchoalveolar Lavage Fluid; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D011510:Proteolipids / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012996:Solutions; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D011510:Proteolipids; D020543:Proteome; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012996:Solutions; D000515:alpha 1-Antitrypsin; D010450:Endopeptidases