Elastin and collagen degradation products in urine of patients with cystic fibrosis

• Published in: American journal of respiratory and critical care medicine Vol. 152; no. 1; p. 157
• Main Authors: Stone, P J, Konstan, M W, Berger, M, Dorkin, H L, Franzblau, C, Snider, G L
• Format: Journal Article
• Language: English
• Published: United States 01-07-1995
• Subjects: Adult; Amino Acids - urine; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Case-Control Studies; Collagen - metabolism; Cystic Fibrosis - metabolism; Cystic Fibrosis - urine; Desmosine - urine; Elastin - metabolism; Female; Humans; Isodesmosine - urine; Leukocyte Elastase; Male; Neutrophils - chemistry; Pancreatic Elastase - analysis; Receptors, Complement - analysis
• ISSN: 1073-449X
• DOI: 10.1164/ajrccm.152.1.7599816

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.