Cleaved secretory leucocyte protease inhibitor as a biomarker of chymase activity in allergic airway disease.
BACKGROUND
Secretory leucocyte protease inhibitor (SLPI), which is present in many physiological fluids including saliva, sputum and nasal discharge, is the most effective inhibitor of chymase. Previously, we demonstrated that chymase is able to cleave SLPI and that the cleaved portion, cSLPI, is a biomarker of chymase activity.


OBJECTIVE
We investigated the potential of cSLPI as a biomarker of chymase activity in subjects with allergic rhinitis (AR) and asthmatic airway disease.


METHODS
Baseline sputum samples were collected from atopic asthmatics and healthy controls (HC). Nasal lavages (NAL) were performed in subjects with AR both at baseline and following a nasal challenge with allergen or placebo. Levels of cSLPI and chymase were determined by Western analysis, and tryptase and alpha-2 macroglobulin were measured by immunoassay.


RESULTS
As compared with HC, asthmatics showed a significant increase in baseline cSLPI/total SLPI ratios and an increase in chymase levels. There was a high correlation of cSLPI/SLPI ratios to chymase levels in normal individuals and untreated asthmatics. In the NAL of patients with AR, as compared with placebo, allergen challenge increased inflammatory biomarkers, including cSLPI/SLPI ratios, chymase levels, tryptase levels and alpha2-macroglobulin levels. Correlations were observed between cSLPI/SLPI ratios and chymase levels and cSLPI/SLPI ratios and alpha2-macroglobulin levels; no correlation was seen between cSLPI/SLPI ratios and tryptase levels.


CONCLUSIONS
Our data indicate that cSLPI reflects chymase activity in AR and asthma. Hence, cSLPI may serve as a biomarker for disease activity and for monitoring the efficacy of novel anti-inflammatory treatments in chymase-mediated diseases.
Belkowski
S M
SM
Johnson and Johnson Pharmaceutical Research and Development, Spring House, PA 19477, USA. sbelkows@its.jnj.com
Boot
J D
JD
Mascelli
M A
MA
Diamant
Z
Z
de Garavilla
L
L
Hertzog
B
B
Polkovitch
D
D
Towers
M
M
Batheja
A
A
D'Andrea
M R
MR
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D053818:Chymases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000737:chemistry / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D012189:Retrospective Studies; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000276:immunology / Q000378:metabolism*; D013183:Sputum / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D015415:Biomarkers; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D000511:alpha-Macroglobulins; D053818:Chymases; D053802:Tryptases