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Updated: Dec 30, 2025
A Simple and Efficient Method to Isolate Macrophages from Mixed Primary Cultures of Adult Liver Cells
Published on: May 24, 2011
Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets
Carsten Deppermann1,2,3, Rachel M Kratofil1,2, Moritz Peiseler1,2
1Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
Abstract:
Every day, megakaryocytes produce billions of platelets that circulate for several days and eventually are cleared by the liver. The exact removal mechanism, however, remains unclear. Loss of sialic acid residues is thought to feature in the aging and clearance of platelets. Using state-of-the-art spinning disk intravital microscopy to delineate the different compartments and cells of the mouse liver, we observed rapid accumulation of desialylated platelets predominantly on Kupffer cells, with only a few on endothelial cells and none on hepatocytes. Kupffer cell depletion prevented the removal of aged platelets from circulation. Ashwell-Morell receptor (AMR) deficiency alone had little effect on platelet uptake. Macrophage galactose lectin (MGL) together with AMR mediated clearance of desialylated or cold-stored platelets by Kupffer cells. Effective clearance is critical, as mice with an aged platelet population displayed a bleeding phenotype. Our data provide 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 compartment.
Insights
Kupffer cells in the liver clear aged platelets by recognizing their loss of sialic acid. The macrophage galactose lectin (MGL) and Ashwell-Morell receptor (AMR) collaborate to remove these desialylated platelets, preventing bleeding.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Megakaryocytes produce billions of platelets daily, which circulate and are eventually cleared by the liver.
- The precise mechanism of platelet removal from circulation remains largely unknown.
- Loss of sialic acid residues on platelets is hypothesized to be a key factor in their aging and clearance.
Purpose of the Study:
- To investigate the cellular mechanisms and receptors involved in the clearance of aged and desialylated platelets in the liver.
- To determine the role of Kupffer cells and specific receptors in platelet removal.
Main Methods:
- Utilized spinning disk intravital microscopy in mice to visualize liver microcirculation and cell interactions.
- Employed Kupffer cell depletion and Ashwell-Morell receptor (AMR) and Macrophage Galactose Lectin (MGL) deficient mouse models.
- Analyzed the accumulation and clearance of desialylated and cold-stored platelets.
Main Results:
- Desialylated platelets rapidly accumulated on Kupffer cells, with minimal interaction with endothelial cells or hepatocytes.
- Depletion of Kupffer cells significantly impaired the clearance of aged platelets.
- Combined deficiency of MGL and AMR receptors hindered the clearance of desialylated platelets by Kupffer cells.
- Mice with aged platelet populations exhibited a bleeding phenotype.
Conclusions:
- Kupffer cells are the primary hepatic cells responsible for clearing desialylated platelets.
- The macrophage galactose lectin (MGL) and Ashwell-Morell receptor (AMR) on Kupffer cells cooperate to mediate the clearance of desialylated platelets.
- Efficient platelet clearance is crucial for maintaining hemostasis and preventing bleeding disorders.
