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Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 1972-1978

The Degree of Branching of the Glycans of alpha 1-Acid Glycoprotein in Asthma
A Correlation with Lung Function and Inflammatory Parameters

MICHEL M. VAN DEN HEUVEL, DENNIS C. W. POLAND, CASPER S. DE GRAAFF, ELISABETH C. M. HOEFSMIT, PIETER E. POSTMUS, ROB H. J. BEELEN, and WILLEM VAN DIJK

Departments of Cell Biology and Immunology, and Medical Chemistry, Faculty of Medicine, and Department of Pulmonary Medicine, Academic Hospital, Vrije Universiteit, Amsterdam; and Department of Pulmonary Medicine, Medisch Centrum Alkmaar, Alkmaar, The Netherlands

alpha 1-Acid glycoprotein (AGP) is a plasma protein belonging to the group of acute-phase proteins. It contains five N-linked glycans which, depending on pathophysiologic state, differ in their degree of branching (i.e., in the relative proportions of di-, tri-, and tetraantennary glycans). Changes in the degree of branching of these glycans have been shown to affect various immunomodulatory properties of AGP. We wanted to investigate whether changes occur in the branching of AGP glycans in plasma and in bronchoalveolar lavage fluid (BALF) in asthma. For this purpose, we selected three groups of patients for study: patients with atopic asthma (AA), atopic nonasthmatic patients, and a group of patients with various interstitial lung diseases (ILDs). The plasma AGP concentration was normal in both atopic study groups, but was increased in ILD patients. In contrast, the branching of glycans of AGP was altered in subjects with AA, whereas it was normal in the other study groups. The presence of asthma symptoms correlated with the increased glycan branching of AGP in both plasma and BALF. Additionally, the degree of branching of AGP in BALF was related to FEV1, to the provocative dose of histamine causing a 20% decrease in FEV (PD20), and to the number of eosinophils. In conclusion, asthma is accompanied by changes in the branching of AGP glycans that indicate an inflammatory reaction that differs markedly from a normal acute-phase response, in which decreased branching of AGP occurs.




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