Glycoprotein IIb-IIIa-liposomes bind fibrinogen but do not undergo fibrinogen-mediated aggregation
Bibliographic record
Abstract
Although platelet cross-bridging is mediated primarily by the binding of fibrinogen to its activated membrane receptor, glycoprotein (GP) IIb-IIIa*, such an interaction may not be sufficient to support the aggregation process. As this question could potentially be answered by reconstituting GPIIb-IIIa* into a non-platelet environment such as liposomes, a protocol was developed for the generation of large lipid vesicles containing purified GPIIb-IIIa*. Flow cytometric techniques confirmed that the receptor was present in the lipid bilayer and were used to evaluate the characteristics of fibrinogen binding to the liposomes, which like fibrinogen-platelet interactions exhibited specificity, saturability, time dependence and calcium dependence. No fibrinogen-specific aggregation of GPIIb-IIIa* liposomes with stir or shear was observed, as determined by flow cytometric cell counting and microscopic examination of particles. In contrast, activated platelets rapidly bound Fg and rapidly formed large aggregates. The Fg associated with GPIIb-IIIa* in liposomes was 'normally' recognized by two fluorescently labelled antibodies: 4A5, which interacts with the Fg gamma chain C-terminus (residues 400-411) required for Fg-mediated cross-bridging of activated platelets in platelet aggregation (Shiba E, Lindon JN, Kushner L, Matsueda GR, Hawiger J, Kloczewiak M, Kudryk B, Salzman EW. Antibody-detectable changes in fibrinogen adsorption affecting platelet activation on polymer surfaces. Am J Physiol 1991; 260: C965-74), and anti-Fg-RIBS-I, which associates with an epitope on Fg (residues 373-385) expressed upon binding to GPIIb-IIIa. These data suggest that the Fg gamma-terminus is sterically accessible for particle cross-bridging and that an identical conformational change occurs for receptor-bound Fg on both liposomes and platelets. It thus appears that cellular elements aside from GPIIb-IIIa, such as cytoskeletal proteins proposed to be necessary for receptor 'anchoring', play a necessary role in flow-associated platelet aggregation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".