Natural α-galactoside- and β-glucoside-specific antibody immune
complexes bound to surface O-glycoproteins of circulating platelets
prevent aggregation, but dislodge at diabetic glucose levels
Abstract
Human anti-α-galactoside (anti-Gal) and anti-β-glucoside (ABG)
antibodies were reported to recognize as surrogate antigens the serine-
and threonine-rich peptide sequences (STPS) in newly detected
albumin-associated O-glycoproteins AOP1 and AOP2 to form circulating
antibody-AOP1/AOP2-albumin triplets. Since triplet antibodies still
possessed unoccupied binding sites, their binding to the
O-glycoprotein-rich platelet surface was examined. Upon treatment with
sugars specific to the above antibodies, freshly harvested normal human
platelets released triplets identical with plasma triplets. The
resulting denuded platelets, unless pre-treated with fibrinogen or the
O-glycan-binding lectin jacalin, recaptured the sugar-extracted
triplets, plasma triplets and isolated triplet antibodies.
Antibody-specific sugars inhibited recapture, confirming that
recognition of STPS on O-glycosylated fibrinogen receptors by antibodies
facilitated triplet attachment to platelets. More triplets were
platelet-bound than in plasma. The dominant jacalin-binding subunit in
triplet-free platelet membrane had size (116 kDa), close to around 120
kDa reported for the O-glycosylated GPIIb subunit of GPIIb/IIIa, the
most expressed and fibrinogen-binding platelet protein. Denuded but not
native platelets were prone to slow spontaneous aggregation and to quick
ADP-mediated GPIIb/IIIa-dependent aggregation unless pre-treated with
jacalin. Amyloid β (Aβ-42 monomer), reported to recognize STPS in plasma
AOP1 and AOP2, but not albumin, bound to triplets in normal platelets
and to membrane O-glycoproteins in denuded ones. ABG-specific sugar
glucose at diabetic concentrations denuded the platelets since sugar
specific to either antibody released triplets of both. Data suggest a
molecular mechanism for diabetes-driven platelet aggregation and how
platelet-leukocyte adhesion and cerebral amyloid angiogenesis, both
requiring exposed GPIIb/IIIa on platelets, may accompany diabetes.