Antiprotease function of airway secretions in purulent tracheobronchitis.
OBJECTIVE
Unopposed activity of the serine protease, human leukocyte elastase (HLE), is detectable in the airways of patients with purulent tracheobronchitis. The aim of this study was to assess the compartmentalization of HLE activity in the liquid sol phase and the solid gel phase of airway secretions.


METHODS
Seventy samples of tracheobrochial aspirates were obtained from patients who had hypersecretion and were receiving mechanical ventilation.


METHODS
Samples were separated into sol and gel ("mucous pellet") phases, and HLE activity was measured using chromogenic substrate degradation. HLE was eluted from the mucous pellet using hypertonic saline solution, 1 mol/L, or bovine pancreatic deoxyribonuclease (DNase), 16 micromol/L.


RESULTS
HLE activity partitioned between the sol and gel phases of the secretions, with most of the activity present in the gel phase (32:1 ratio of gel to sol HLE activity). The activity of HLE was 95% inhibited when bound to the gel phase, but activity appeared to be largely restored after elution from the gel phase. The gel phase was capable of binding additional exogenous HLE, and its binding capacity for exogenous HLE was not saturated by concentrations that exceeded the highest clinically relevant HLE levels (1.1 mg/mL). Hypertonic saline solution and DNase I efficiently liberated endogenous and exogenous gel phase-bound HLE activity, suggesting that electrostatic bonds and DNA, respectively, play important roles in binding HLE to the gel phase.


CONCLUSIONS
The solid phase of airway secretions is a more important modulator of elastase-antielastase balance than has been previously recognized.
O'Riordan
Thomas G
TG
Department of Biology, Stony Brook University, NY, USA.
Seischab
Lori B
LB
Ying
Qi-Long
QL
Colon-Carreras
Eliseo
E
Chughtari
Bilal
B
Palmer
Lucy B
LB
Simon
Sanford R
SR
D001991:Bronchitis / Q000503:physiopathology*; D002863:Chromogenic Compounds; D003850:Deoxyribonuclease I / Q000502:physiology; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000502:physiology; D014136:Tracheitis / Q000503:physiopathology*
D002863:Chromogenic Compounds; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D009195:Peroxidase; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I; D019272:Leukocyte Elastase