Proteolysis of surfactant protein D by cystic fibrosis relevant proteases.
Surfactant protein D (SP-D) is an important innate host defense molecule that has been shown to interact with cystic fibrosis (CF)-associated pathogens. Previous studies demonstrated that rat SP-D is highly resistant to degradation by a wide range of proteolytic enzymes. The aim of this study was to examine whether human SP-D can be degraded by CF relevant proteases ex vivo and in vitro. Bronchoalveolar lavage fluids (BALFs) of 11 patients with CF in a stable clinical condition were examined for SP-D by immunoblotting. In vitro, purified human SP-D was treated with human leukocyte elastase, proteinase 3, cathepsin G or Pseudomonas elastase followed by immunoblotting with specific antibodies to SP-D. In BALF of 8 of the 11 patients investigated, proteolytic fragments or absence of SP-D were detected. In vitro proteolysis of SP-D was observed in a time-dependent manner for each protease applied. The presence of Ca(++) at a physiologic concentration delayed, but did not prevent the degradation. We conclude that SP-D is an important target of numerous proteases present in the CF lung. Host defense is probably impaired due to proteolysis of SP-D and may contribute to the suppurative lung disease in CF.
von Bredow
C
C
Lung Research Group, Children's Hospital of Ludwig Maximilians University, Munich, Germany.
Wiesener
A
A
Griese
M
M
D000293:Adolescent; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003550:Cystic Fibrosis / Q000201:enzymology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*
D037663:Pulmonary Surfactant-Associated Protein D; D010447:Peptide Hydrolases