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Cell pathways in lung inflammation and injury
S76 Proteinase 3 activity in sputum from alpha-1-antitrypsin deficient subjects
  1. N J Sinden,
  2. M Ungurs,
  3. R Edgar,
  4. P Bharadwa,
  5. R A Stockley
  1. Queen Elizabeth Hospital, Birmingham, UK

Abstract

Introduction Tissue destruction in emphysema is widely believed to result from an imbalance between serine proteinases and their inhibitors, the antiproteinases. Previous work has studied the role of neutrophil elastase (NE), but there are few studies of proteinase 3 (PR3). PR3 is released from activated neutrophils concurrently with NE, is more abundant than NE and has fewer airway inhibitors. PR3, unlike NE, is not inhibited by secretory leukoproteinase inhibitor (SLPI). Some studies that have reported “elastase” activity in airway secretions have potentially measured the combined activities of PR3 and NE. Our hypothesis is that PR3 plays a more important role in the tissue damage of emphysema than has previously been considered.

Methods Twenty-eight clinically stable patients with α-1-antitrypsin deficiency (A1ATD) were selected with the PiZZ phenotype and chronic bronchitis. The mean age was 55.8 years and 82% were male. All subjects had full pulmonary function tests and quality of life scores as measured by the St George's Respiratory Questionnaire (SGRQ). Spontaneously produced sputum was collected for microbiology, and the sol-phase was obtained by ultracentrifugation. PR3 and NE activities were measured in all of the samples using specific substrates. The following measurements were taken in a selection of samples; myeloperoxidase (MPO), interleukin (IL)-8, and leukotriene (LT)-B4. A selection of patients had CT densitometry performed.

Results In the sample of patients studied, PR3 activity was detected in all of the sol-phase sputum samples (mean 323.90 nm, SEM 72.46) whereas NE activity was detected in only 6 of the samples (overall mean 196.42 nm, SEM 100.59). PR3 activity correlated with IL-8 concentration (p=0.004), NE activity (p=0.001) and total pathogenic bacterial load (p=0.001). There was no significant correlation with myeloperoxidase or LTB4 concentrations. PR3 activity correlated with SGRQ total score (p=0.001) but no correlation was found with lung function parameters or CT densitometry.

Conclusion This pilot study is the first to directly measure PR3 activity in sol-phase sputum. We have shown that PR3 activity can be detected in A1ATD patients, and correlates with the chemoattractant IL-8, NE activity, pathogenic bacterial load and SGRQ total score. PR3 activity should be assessed when evaluating proteinase-mediated airway damage.

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