Abstract Number: PB1624
Meeting: ISTH 2020 Congress
Background: Every day, human megakaryocytes produce billions of platelets that patrol the vasculature for several days. At the end of their lifespan, platelets get cleared in the liver through a process that is incompletely understood. Loss of sialic acid residues is thought to feature in the aging and clearance of platelets. Recent studies suggest that desialylation causes platelet clearance via the Ashwell-Morell receptor (AMR) on hepatocytes, however, this process has never been observed in vivo.
Aims: Therefore, our aim was to study the process of platelet clearance in vivo using intravital microscopy of the mouse liver.
Methods: We performed spinning-disk intravital confocal microscopy of the liver of anesthetized naive mice to observe platelet-Kupffer cell interactions in the steady state. Mice were treated mice with sialidase to induce in vivo desialylation of platelets or transfused with ex vivo desialylated platelets. We also performed flow cytometric and platelet analyses.
Results: We found that under basal conditions, platelets continuously touch down and let go on Kupffer cells. A small percentage of platelets, however, remained attached to the Kupffer cells and were ingested. Similarly, when we desialylated platelets in vivo or ex vivo we observed rapid accumulation almost exclusively on Kupffer cells but not on hepatocytes or endothelium. Combining AMR deficiency with blocking the macrophage galactose lectin (MGL) resulted in almost completely abolished adhesion of desialylated platelets to Kupffer cells and their subsequent uptake. This process was also relevant for the clearance of cold-stored platelets. Interrupting platelet clearance by depleting Kupffer cells led to the accumulation of aged platelets and increased bleeding.
Conclusions: Our data provides evidence that the MGL of Kupffer cells plays a significant role in the removal of desialylated platelets through a collaboration with the AMR thereby maintaining a healthy and functional platelet population.
To cite this abstract in AMA style:Deppermann C, Kratofil RM, Peiseler M, David BA, Zindel J, Castanheira FVES, van der Waal F, Carestia A, Jenne CN, Marth JD, Kubes P. Kupffer Cells Clear Aged Platelets through Macrophage Galactose Lectin [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/kupffer-cells-clear-aged-platelets-through-macrophage-galactose-lectin/. Accessed August 19, 2022.
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