Exposure of platelet fibrinogen receptors by a monoclonal antibody to CD9 antigen.

Abstract

We found that a monoclonal antibody to CD9 antigen, PMA2, induces fibrinogen binding to platelets and examined the mechanism for this. That PMA2 recognized the CD9 antigen was confirmed by its immunoblot-reactivity with a 24,000-dalton protein, reactivity with platelets and common acute lymphoblastic leukemia (ALL) cells, and competitive binding with the ALB6 antibody known as the CD9 antibody. At saturation, PMA2 bound to approximately 46,000 sites per platelet. The binding of 125I-fibrinogen to platelets occurred in a PMA2 concentration-dependent manner and was blocked by EDTA or an anti-glycoprotein (GP)IIb-IIIa monoclonal antibody. PMA2-stimulated platelets caused ATP secretion and thromboxane B2 synthesis under non-stirred conditions. The role of secreted ADP and thromboxane in fibrinogen-binding and subsequent platelet aggregation was studied using creatine phosphate/creatine phosphokinase (CP/CPK) and aspirin. CP/CPK or aspirin alone reduced fibrinogen binding to 20% to 30%; however, this binding was sufficient to support full platelet aggregation. Combined treatment with CP/CPK and aspirin abolished fibrinogen binding and aggregation. These results demonstrate that the binding of IgG molecules to the CD9 antigen exposes fibrinogen receptors through both secreted ADP and thromboxane and that either one of both can expose the receptors to an extent sufficient to aggregate platelets.

• Authors: T Hato, K Ikeda, M Yasukawa, A Watanabe, Y Kobayashi
• Journal: Blood (Blood) Vol. 72 Issue 1 Pg. 224-9 (Jul 1988) ISSN: 0006-4971 [Print] United States
• PMID: 2455569 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Antigens, Differentiation
• CD9 protein, human
• Cd9 protein, mouse
• Epitopes
• Membrane Glycoproteins
• Platelet Membrane Glycoproteins
• Tetraspanin 29
• Phosphocreatine
• Thromboxane B2
• Fibrinogen
• Aspirin

Topics

• Animals
• Antibodies, Monoclonal (physiology)
• Antigen-Antibody Reactions
• Antigens, CD
• Antigens, Differentiation (immunology)
• Aspirin (pharmacology)
• Binding Sites, Antibody
• Blood Platelets (immunology, metabolism, physiology)
• Epitopes (immunology)
• Fibrinogen (metabolism)
• Humans
• Membrane Glycoproteins
• Mice
• Mice, Inbred BALB C
• Phosphocreatine (pharmacology)
• Platelet Aggregation (drug effects)
• Platelet Membrane Glycoproteins (drug effects, immunology, metabolism)
• Tetraspanin 29
• Thromboxane B2 (biosynthesis)