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PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes
E Larsen1, A Celi, G E Gilbert
1Division of Hematology/Oncology, New England Medical Center, Boston, Massachusetts.
Abstract:
PADGEM (platelet activation dependent granule-external membrane protein) is an integral membrane protein of the alpha granules of platelets and Weibel-Palade bodies of endothelial cells that is expressed on the plasma membrane upon cell activation and granule secretion. Activated platelets, but not resting platelets, bind to neutrophils, monocytes, HL60 cells, and U937 cells. This interaction is inhibited by anti-PADGEM antibodies, PADGEM, and EDTA; anti-GPIIb-IIIa, anti-thrombospondin, anti-GPIV, and thrombospondin produce no effect. Neutrophils and U937 cells, in contrast to Jurkatt cells, contain PADGEM recognition sites, as shown by binding of PADGEM contained in phospholipid vesicles. These results indicate that PADGEM mediates adhesion of activated platelets to monocytes and neutrophils. Therefore, PADGEM shares not only structural but also functional homology with ELAM-1 and MEL-14, members of a new family of vascular cell adhesion molecules.
Insights
Platelet activation dependent granule-external membrane protein (PADGEM) mediates activated platelet adhesion to neutrophils and monocytes. PADGEM functions similarly to other vascular cell adhesion molecules.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Platelet activation dependent granule-external membrane protein (PADGEM) is found in platelet alpha granules and endothelial Weibel-Palade bodies.
- PADGEM is expressed on the cell surface after activation and granule release.
Purpose of the Study:
- To investigate the role of PADGEM in cell adhesion.
- To determine if PADGEM mediates the binding of activated platelets to other cell types.
Main Methods:
- Studied the binding of activated platelets to neutrophils, monocytes, HL60 cells, and U937 cells.
- Investigated the inhibitory effects of anti-PADGEM antibodies, PADGEM, and EDTA on this interaction.
- Assessed the presence of PADGEM recognition sites on various cell types using phospholipid vesicles containing PADGEM.
Main Results:
- Activated platelets bind to neutrophils and monocytes, but not resting platelets.
- This interaction is specifically inhibited by anti-PADGEM antibodies, PADGEM, and EDTA.
- Neutrophils and U937 cells possess PADGEM recognition sites, indicating PADGEM mediates platelet adhesion to these cells.
Conclusions:
- PADGEM is a key mediator of activated platelet adhesion to monocytes and neutrophils.
- PADGEM exhibits functional and structural similarities to ELAM-1 and MEL-14, suggesting it belongs to a new family of vascular cell adhesion molecules.
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