High glucose removes natural anti‑α‑galactoside and anti‑β‑glucoside antibody immune complexes adhering to surface O‑glycoproteins of normal platelets and enhances platelet aggregation

Karthi,Sreedevi; Sukumari‑Ramesh,Sangeetha; Geetha,Mandagini; Appukuttan,Padinjaradath Sankunni

doi:10.3892/etm.2021.11005

High glucose removes natural anti‑α‑galactoside and anti‑β‑glucoside antibody immune complexes adhering to surface O‑glycoproteins of normal platelets and enhances platelet aggregation

Authors:
- Sreedevi Karthi
- Sangeetha Sukumari‑Ramesh
- Mandagini Geetha
- Padinjaradath Sankunni Appukuttan
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Affiliations: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695011, India
Published online on: November 25, 2021 https://doi.org/10.3892/etm.2021.11005
Article Number: 82
Copyright: © Karthi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human natural anti‑α‑galactoside (anti‑Gal) and anti‑β‑glucoside (ABG) antibodies were previously reported to recognize the serine‑ and threonine‑rich peptide sequences (STPS) of albumin‑associated O‑glycoproteins (AOP1 and AOP2) as surrogate antigens, forming anti‑Gal/ABG‑AOP1/AOP2‑albumin triplet immune complexes in plasma. Since antibodies in these triplets still possessed unoccupied binding sites, the presence of triplets on human platelets that abound in surface O‑glycoproteins was examined. Upon treatment with α‑galactosides and β‑glucosides, normal platelets freshly isolated from young healthy individuals released triplets identical with plasma triplets according to ELISA results. The resulting denuded platelets, unless pre‑treated with fibrinogen or the O‑glycan‑binding lectin jacalin, recaptured these sugar‑extracted triplets in the absence of antibody‑specific sugars, suggesting that the triplet antibodies recognized the STPS of O‑glycosylated receptors on platelets. Molecular weight of the dominant jacalin‑binding subunit on triplet‑free platelet membrane was 116 kDa, close to the ~120 kDa reported for the IIb subunit of the most abundant fibrinogen‑binding platelet O‑glycoprotein, GPIIb/IIIa. Denuded, but not native, platelets underwent slow spontaneous aggregation and rapid ADP‑mediated GPIIb/IIIa‑dependent aggregation according to spectrophotometric assay. Pre‑treatment of denuded platelets with jacalin significantly reduced their ADP‑mediated aggregation. Amyloid β (Aβ‑42 monomer) was reported to bind triplet O‑glycoproteins through their STPS but not to albumin or the antibodies. This peptide bound to the triplets on normal platelets and to surface membrane O‑glycoproteins on denuded platelets, suggesting that the surface O‑glycoproteins on the normal platelets were engaged and masked by the triplets. The ABG‑specific sugar glucose denuded the platelets at concentrations typically reached in diabetic sera, since anti-Gal specific or ABG-specific sugar released the triplets of both the antibodies from the platelets. In conclusion, the present study offered rationale for the presence of anti‑Gal/ABG‑O‑glycoprotein‑albumin triplets on normal platelets, for the role of triplets in platelet physiology amidst circulating platelet‑activating factors such as ADP, and for platelet vulnerability during diabetes.

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