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Reproducibility and Harmonization in Research Using Biological Standards: The Example of Platelet Agonist Collagen-Related Peptide
Published on: August 4, 2023
Collagen response and glycoprotein VI function decline progressively as canine platelets age in vivo
L Alberio1, P Friese, K J Clemetson
1Department of Medicine, W. K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Thrombosis and Haemostasis
|September 28, 2002
Summary
Platelet function declines with age, with aged canine platelets becoming less responsive to collagen and its receptor, glycoprotein VI (GPVI). This age-related decline appears to be influenced by external factors affecting GPVI.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Platelet function is known to decrease with cell age.
- Previous studies found only minor biochemical changes in aged platelets.
- The specific mechanisms of age-dependent platelet dysfunction remain unclear.
Purpose of the Study:
- To investigate age-dependent alterations in canine platelet response to collagen.
- To identify changes in collagen receptor glycoprotein VI (GPVI) function during platelet aging.
- To explore potential extrinsic factors influencing platelet aging and collagen responsiveness.
Main Methods:
- Assessed collagen response in aged canine platelets using collagen types I, III, and V.
- Utilized convulxin, a specific GPVI agonist, to measure platelet activation and binding.
- Investigated platelet function in a unique dog (#428) with sustained convulxin reactivity.
- Performed platelet transfusion experiments to evaluate extrinsic influences on aging.
Main Results:
- Aged canine platelets showed increased EC50 for collagen and a refractory population.
- Convulxin-induced platelet activation and binding declined with age, with loss of high-affinity binding.
- Dog #428 platelets maintained high convulxin reactivity throughout their lifespan.
- Transfused platelets into dog #428 did not exhibit expected age-dependent functional decline.
Conclusions:
- Canine platelet response to collagen is significantly dependent on cell age.
- The functional decline is partly mediated by extrinsic factors, potentially proteolytic, affecting GPVI.
- Platelet aging involves complex alterations in receptor function and responsiveness.
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