Studies on the dual effects on platelets of a monoclonal antibody to CD9, and on the properties of platelet CD9

The article describes effects on human platelets of a murine monoclonal ant ibody of the IgG2a subtype (clone FN99) directed against the membrane glyco protein CD9. This antibody exerts a dual action on human platelets in plasm a depending on whether the complement system can be activated or not, resul ting either in membrane permeabilization or a true platelet aggregation. Se cretion from the alpha-granules during permeabilisation was not observed in the sense that the granule-located protein thrombospondin was retained in the platelets, as opposed to what was seen with platelets that had undergon e an antibody-induced aggregation. Only a small fraction of P-selectin was found on the surface of the permeabilised platelets. The cytoskeletal prote in actin-binding protein (filamin) was profoundly degraded during membrane permeabilisation. however, and scanning electron microscopy showed platelet s that were swollen with only a few pseudopodia. Preincubation of platelets with three different antibodies to CD9 showed strong inhibition of a subse quent binding of FITC-labelled Fab fragment of FN99 indicating that antibod ies tend to bind in the same area of the CD9 molecule. No association of CD 9 to the platelet actin-based cytoskeleton was observed. CD9 was present on the surface of microvesicles derived from calcium ionophore-treated platel ets. (C) 1999 Elsevier Science Ltd. All rights reserved.