title: Elastin and collagen degradation products in urine of patients with cystic fibrosis.
abstract: Elastin degradation has been reported to be increased in patients with cystic fibrosis (CF). In order to further explore evidence for elastin degradation in a group of 18 patients with CF with a wide range of disease severity, we used an isotope dilution method to measure urinary desmosine (DES) and isodesmosine (IDES), amino acids derived exclusively from cross-linked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), amino acids derived exclusively from cross-linked collagen. Urinary DES and IDES (mean +/- SD) were 23.9 +/- 30.7 and 18.5 +/- 22.4 micrograms/g creatinine, respectively, in the patients with CF versus 7.5 +/- 1.7 and 6.8 +/- 1.4 micrograms/g creatinine, respectively, in 10 healthy control subjects (p < 0.001); only two patients with CF had DES values within the control range. The values of urinary HP and LP in the CF group were 54.9 +/- 39.1 and 12.3 +/- 8.6 nmol/mmol creatinine, respectively, versus 24.5 +/- 5.8 and 5.1 +/- 2.7 nmol/mmol creatinine, respectively, in the controls (p < 0.005). Both HP and LP were highly correlated (r = 0.71, p < 0.0001). Patients with CF had active pulmonary inflammation; neutrophils were abundant in the bronchoalveolar lavage fluid of the CF group and correlated with elastase activity measured with methoxysuccinyl Ala-Ala-Pro-Val paranitroanilide (r = 0.61, p < 0.05). Airway neutrophils had decreased expression of the complement receptor CR1 (CR1/CR3 of 0.17 +/- 0.15 versus 1.0 for blood neutrophils), a change known to be caused by uninhibited neutrophil elastase. We conclude that lung elastin is the most likely source of the increased DES and IDES in CF.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Stone
authors.forename: M W
authors.initials: MW
authors.lastname: Konstan
authors.forename: M
authors.initials: M
authors.lastname: Berger
authors.forename: H L
authors.initials: HL
authors.lastname: Dorkin
authors.forename: C
authors.initials: C
authors.lastname: Franzblau
authors.forename: G L
authors.initials: GL
authors.lastname: Snider
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000652:urine*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism / Q000652:urine*; D003895:Desmosine / Q000652:urine; D004549:Elastin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007524:Isodesmosine / Q000652:urine; D019272:Leukocyte Elastase; D008297:Male; D009504:Neutrophils / Q000737:chemistry; D010196:Pancreatic Elastase / Q000032:analysis; D011951:Receptors, Complement / Q000032:analysis
chemical_list: D000596:Amino Acids; D011951:Receptors, Complement; D003895:Desmosine; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen; D004549:Elastin; D007524:Isodesmosine; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase