| Deciphering platelet cold storage lesion in hibernating rodents Scott Cooper. |
Abstract
Natural hibernators such as the 13-lined ground squirrel undergo extensive physiological changes during hibernation while alternating between periods of torpor and brief interbout arousals. During torpor, their heart rate and body temperature decrease, they have decreased circulating platelet counts, and these platelets undergo structural changes resulting in a rod confirmation. Furthermore, the cooling of ground squirrel platelets does not impact their clearance rate from circulation post-transfusion, whereas chilled human platelets are rapidly cleared from circulation. Since cold-stored human platelets are rapidly cleared from circulation post-transfusion, they must be stored at room temperature, limiting their shelf-life to 5 days due to microbial contamination. To investigate the mechanisms involved in the clearance of cold-stored human platelets, human and ground squirrel platelets were stored at room-temperature or 4oC before being analyzed for changes in apoptosis, phagocytosis rates by HepG2 cells, and surface receptor desialylation. As expected, human platelets stored at 4oC displayed progressive increases in phosphatidylserine surface exposure and caspase activation, indicative of apoptosis, while ground squirrel platelets showed minimal change. Additionally, while cold storage caused increased rates of phagocytosis by HepG2 cells of human platelets, ground squirrel platelets showed lower rates of phagocytosis, with taxol treated ground squirrel platelets showing the lowest phagocytosis rates between both species and all treatments. Furthermore, following cold storage, sialic acid residues on human platelets were being removed, while the terminal sialic acid residues on ground squirrel platelets remained unaffected. These results suggest that ground squirrel platelets may be resistant to apoptosis, capable of avoiding phagocytosis by hepatocytes, and resist cold storage lesions by avoiding sialic acid removal. Although these experiments were in vitro, they do provide possible explanations as to how platelets can survive hibernation and can function following arousal.
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