Molecular architecture and platelet-activating properties of small immune complexes assembled on heparin and platelet factor 4.
Commun Biol
; 7(1): 308, 2024 Mar 11.
Article
en En
| MEDLINE
| ID: mdl-38467823
ABSTRACT
Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin leading to a reduction in circulating platelets with an increased risk of thrombosis. It is precipitated by polymerized immune complexes consisting of pathogenic antibodies that recognize a small chemokine platelet factor 4 (PF4) bound to heparin. Characterization of these immune complexes is extremely challenging due to the enormous structural heterogeneity of such macromolecular assemblies and their constituents. Native mass spectrometry demonstrates that up to three PF4 tetramers can be assembled on a heparin chain, consistent with the molecular modeling studies showing facile polyanion wrapping along the polycationic belt on the PF4 surface. Although these assemblies can accommodate a maximum of only two antibodies, the resulting immune complexes are capable of platelet activation despite their modest size. Taken together, these studies provide further insight into molecular mechanisms of HIT and other immune disorders where anti-PF4 antibodies play a central role.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trombocitopenia
/
Heparina
Límite:
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article