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 antibody of the IgG2a subtype (clone FN99) directed against the membrane glycoprotein CD9. This antibody exerts a dual action on human platelets in plasma depending on whether the complement system can be activated or not, resulting either in membrane permeabilization or a true platelet aggregation. Secretion 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 undergone an antibody-induced aggregation. Only a small fraction of P-selectin was found on the surface of the permeabilised platelets. The cytoskeletal protein actin-binding protein (filamin) was profoundly degraded during membrane permeabilisation, however, and scanning electron microscopy showed platelets that were swollen with only a few pseudopodia. Preincubation of platelets with three different antibodies to CD9 showed strong inhibition of a subsequent binding of FITC-labelled Fab fragment of FN99 indicating that antibodies tend to bind in the same area of the CD9 molecule. No association of CD9 to the platelet actin-based cytoskeleton was observed. CD9 was present on the surface of microvesicles derived from calcium ionophore-treated platelets.
Inngjerdingen
M
M
Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway.
Waterhouse
K
K
Solum
N O
NO
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology* / Q000473:pathology*; D002462:Cell Membrane / Q000276:immunology; D002463:Cell Membrane Permeability; D003594:Cytoplasmic Granules / Q000276:immunology / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins; D019007:P-Selectin / Q000276:immunology; D010974:Platelet Aggregation / Q000187:drug effects / Q000276:immunology*; D060245:Tetraspanin 29
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D019007:P-Selectin; D060245:Tetraspanin 29