Effects of variant gamma chains and sialic acid content of fibrinogen upon
its interactions with ADP-stimulated human and rabbit platelets
EJ Harfenist, MA Packham and JF Mustard
When platelets are stimulated with adenosine diphosphate (ADP), fibrinogen
binds to receptors on the platelet membrane, and the platelets aggregate.
The primary platelet recognition sites of human fibrinogen are reported to
be at the COOH-terminal ends of the gamma chains, with secondary sites in
the A alpha chains. Normal human fibrinogen, which consists of three pairs
of disulfide-bonded peptide chains, (A alpha, B beta, gamma)2, is
heterogeneous with respect to sialic acid content and also contains a small
proportion of molecules with a variant gamma chain (designated gamma'),
elongated by a peptide extension at the COOH-terminus of the normal gamma
chain. We separated fibrinogen into three fractions by chromatography on
DEAE cellulose and tested the interactions of these fractions with
ADP-stimulated human and rabbit platelets. Two fractions had the normal
chain composition, (A alpha B beta, gamma)2, but different sialic acid
contents (6.6 and 7.2 mol/mol), and the third fraction had the chain
composition (A alpha, B beta)2 gamma gamma' and a sialic acid content of
7.2 mol/mol, which is similar to that of one of the normal fractions. In
binding and aggregation experiments, we detected no significant differences
between the reactions of the first two fractions, but ADP-stimulated
platelets bound only 50% as much of 125I-fibrinogen from the fraction with
the gamma' chains and also aggregated less extensively in the presence of
this fraction. We conclude that the sialic acid content of fibrinogen does
not significantly affect its interactions with platelets, but the elongated
gamma' chains bind less effectively to ADP-stimulated platelets, and thus
reduce the ability of fibrinogen to support aggregation. This may result
from a conformational change caused by the gamma' extension or from the
deletion of a portion of the normal gamma chain recognition site.
Volume 64,
Issue 6,
pp. 1163-1168,
12/01/1984
Copyright © 1984 by The American Society of Hematology
