Am. J. Respir. Crit. Care Med., Vol 154, No. 4, Oct 1996, 952-958.
Altered composition of urinary heparan sulfate in patients with COPD
CH van de Lest, EM Versteeg, JH Veerkamp, JH Berden, J van den Born, L Heunks, JW Lammers, CL van Herwaarden, PN Dekhuijzen and TH van Kuppevelt
Department of Biochemistry, University of Nijmegen, the Netherlands.
In patients with emphysema the integrity of the extracellular matrix
(connective tissue skeleton) is compromised. In this study we analyzed
glycosaminoglycans, which are main constituents of this matrix, in urines
from patients with chronic obstructive pulmonary disease (COPD)/emphysema.
Glycosaminoglycans (GAGs) were purified by anion exchange chromatography
and quantified using the 1,9-dimethylmethylene blue assay. Heparan sulfate
(HS) was assayed using three different chemical methods: digestion with
heparitinase or with nitrous acid and by use of an adapted
1,9-dimethylmethylene blue assay. A specific epitope on the HS molecule,
defined by the monoclonal antibody JM403, was determined using an
inhibition enzyme immunoassay. In patients with COPD total urinary
glycosaminoglycan and HS content were not altered. The JM403 epitope of HS,
however, was greatly decreased in patients (0.6 versus 4.1 units/mg
creatinine for control subjects, p < 0.0001). A similar pattern was
observed when patients with bronchial carcinoma with and without emphysema
were compared (0.4 versus 2.4 units/mg creatinine respectively, p <
0.0005). Patients with sarcoidosis did not show a decreased epitope
content. These results indicate a structural change or an altered
processing of the HS molecule in patients with emphysema. Taking into
consideration the importance of HS for the stability of the alveolar
extracellular matrix, this change may be associated with the pathogenesis
of emphysema.
