Introduction
A fraction of circulating human albumin molecules are
non-covalently attached to either of two newly detected heavily
O-glycosylated proteins AOP1(107 kDa) and AOP2 (98 kDa) [1]. Nearly
all plasma anti-α-galactoside (anti-Gal) and anti-β-glucoside (ABG)
antibodies are bound to the albumin-associated AOP1 or AOP2 to form
antibody-AOP1/AOP2-albumin triplets [1] due to recognition of the
serine-and threonine-rich peptide sequences (STPS) of the
O-glycoproteins as surrogate ligand by either antibody
[2]. Unlike purified albumin, the isolated
O-glycoproteins, their albumin complexes and triplet immune complexes
could bind to amyloid β peptide (Aβ-42) [3] that also recognizes
STPS. While isolated AOP1 or AOP2 occupied all available binding sites
on either antibody, albumin-bound AOP1 or AOP2 occupied these sites only
partially during triplet formation, apparently for steric reasons.
Utilizing their spared binding sites the triplets could bind in turn to
antibody-specific ligands in affinity matrices [1] and activated
macrophages (our unpublished data) possibly because the STPS in the
latter are more accessible than in albumin-bound AOP1/AOP2.
Factors that prevent platelet-activating blood factors such as ADP
and fibrinogen from causing haphazard platelet activation are poorly
known. Notably GPIIb/IIIa, which is the most abundantly expressed
protein on platelet surface, the receptor for fibrinogen and a link in
the ADP-mediated platelet activation cascade and
aggregation, is heavily O-glycosylated and therefore
rich in STPS on its IIb subunit [4]. Also, platelets are reported to
bear on their surface, immunoglobulins and albumin in the same ratio
(1:1) as in triplets [5] and are major carriers of amyloid β [6]
that also binds to triplet O-glycoproteins [3]. This paper presents
evidence for the presence of anti-Gal/ABG-AOP1/AOP2-albumin triplets,
anchored through the unutilized binding sites on their antibodies, on
the surface of normal human platelets using STPS of O-glycoprotein(s) on
the latter as ligands. It also examines the consequences of depriving
platelets of their triplet cover.