Characterization of peptide fragments from lung elastin degradation in chronic obstructive pulmonary disease.
This study presents a method for detecting and characterizing peptides of elastin that result from lung matrix injury in chronic obstructive pulmonary disease (COPD). Lung elastin degradation was studied by two representative in vivo elastases, human neutrophil elastase (HNE) and macrophage metalloproteinase (MMP12). The resulting peptide mixtures were analyzed by high-performance liquid chromatography/electrospray tandem mass spectrometry (LC/MSMS) to characterize 40 elastin-derived peptides (EDPs), 24 from HNE and 16 from MMP12 digestions. The peptides constitute major EDPs that are solubilized by the enzymatic digestion. Using the selected reaction monitoring (SRM) from LC/MSMS analysis, the transition ions of the peptides were used to investigate the presence of the peptides in selected body fluids of chronic obstructive pulmonary disease (COPD) patients. Four peptides, GYPI, APGVGV, GLGAFPA, and VGVLPGVPT, were detected in plasma or sputum of some COPD patients but not in normal controls. A hexapeptide VGVAPG, which had been widely studied for its chemotactic activity for a possible pathogenic role in COPD, was not detected in lung EDPs by HNE or MMP12 digestion, but only by porcine pancreatic elastase (PPE) digestion. This study demonstrates a practical methodology to study peptides from matrix degradations in pulmonary disease and a means of investigating their pathogenesis.
He
Jiangtao
J
Department of Medicine, St. Luke's Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York 10019, USA.
Turino
Gerard M
GM
Lin
Yong Y
YY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004549:Elastin / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010449:Peptide Mapping / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D021241:Spectrometry, Mass, Electrospray Ionization; D013183:Sputum / Q000737:chemistry / Q000378:metabolism; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D010446:Peptide Fragments; D004549:Elastin; D019272:Leukocyte Elastase; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12