Preliminary observations on the influence of rheumatoid alpha-1-acid glycoprotein on collagen fibril formation.
This study investigates the effect of alpha(1)-acid glycoprotein (AGP) isolated from both normal and rheumatoid plasma on type II collagen fibril formation. Rheumatoid samples were obtained over 2 years from two patients with early arthritis. The glycosylation of each sample was analysed to establish any correlation with fibrillogenesis. Rheumatoid AGP displays increased fucosylation compared to normal AGP. In both patients the fucosylation dipped after 1 year, then rose again over year 2. It is proposed that year 1 corresponds to the acute phase of the disease and the onset of chronic inflammation after this time produces a subsequent increase in fucosylation. Rheumatoid AGP influences type II collagen fibrillogenesis. Native fibrils were produced but with differences in the rate and extent of fibrillogenesis depending on AGP concentration and fucosylation. Low concentrations produced a decrease in fibrillogenesis rate and fibril diameter. High concentrations produced fibrils at a rate and diameter dependent on fucosylation. Highly fucosylated AGP produced narrow fibrils slowly, whereas poorly fucosylated AGP produced thicker fibrils more quickly. We propose that differences in glycosylation (especially fucosylation) of AGP are responsible for differences in collagen fibrillogenesis and this phenomenon may contribute to the exacerbation of cartilage destruction in rheumatoid arthritis.
Haston
J Louise
JL
Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow G4 0NR, UK.
FitzGerald
Oliver
O
Kane
David
D
Smith
Kevin D
KD
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D005643:Fucose / Q000032:analysis; D006801:Humans; D009391:Nephelometry and Turbidimetry; D009961:Orosomucoid / Q000737:chemistry / Q000378:metabolism*
D009961:Orosomucoid; D005643:Fucose; D003094:Collagen