A paradoxical effect of antibody concentration on vWF-dependent platelet agglutination distinguishes between botrocetin and ristocetin-induced agglutination.
Several heterologous antisera directed against either human or porcine von Willebrand factor (vWF), inhibited botrocetin-induced vWF-dependent agglutination at high concentrations but were found to enhance this reaction at low concentrations. Purified IgG from these immune sera also potentiated botrocetin-induced agglutination as did its F(ab)'2 fragments. However, monovalent Fab fragments of the purified IgG did not. The requirement for a divalent antigen combining region suggests that one possible mechanism of enhanced agglutination may involve intra or inter-molecular cross-linking of vWF multimers by the antibody. Another possible mechanism could be a conformational change in the vWF molecule induced by antibody binding. Such a conformational change may provide additional active sites on the vWF molecule that, in the presence of botrocetin, lead to enhancement of the agglutination reaction. Antisera to human vWF that showed this paradoxical inhibitory/enhancing effect on botrocetin-induced agglutination also inhibited ristocetin-induced platelet agglutination at high concentrations, but failed to enhance agglutination at any concentration. The different effects of these antisera on botrocetin and ristocetin-induced platelet agglutination suggest that no single mechanism can explain the action of both of these mediators.
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000918:Antibody Specificity; D003435:Crotalid Venoms / Q000494:pharmacology*; D006801:Humans; D007106:Immune Sera / Q000032:analysis; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011487:Protein Conformation; D011817:Rabbits; D012310:Ristocetin / Q000494:pharmacology*; D013552:Swine; D014841:von Willebrand Factor / Q000276:immunology / Q000502:physiology*
D000276:Adjuvants, Immunologic; D000906:Antibodies; D003435:Crotalid Venoms; D007106:Immune Sera; D007140:Immunoglobulin Fab Fragments; D014841:von Willebrand Factor; D012310:Ristocetin; C030961:botrocetin