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.
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January 24 2020
Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets
Carsten Deppermann
,
Carsten Deppermann
Conceptualization
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
3
Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Rachel M. Kratofil
,
Rachel M. Kratofil
Formal analysis
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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Moritz Peiseler
,
Moritz Peiseler
Investigation
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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Bruna A. David
,
Bruna A. David
Investigation
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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Joel Zindel
,
Joel Zindel
Investigation
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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Fernanda Vargas E Silva Castanheira
,
Fernanda Vargas E Silva Castanheira
Methodology
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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Fardau van der Wal
,
Fardau van der Wal
Formal analysis
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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Agostina Carestia
,
Agostina Carestia
Methodology
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
4
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
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Craig N. Jenne
,
Craig N. Jenne
Investigation
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
4
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
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Jamey D. Marth
,
Jamey D. Marth
Conceptualization
5
Center for Nanomedicine, SBP Medical Discovery Institute, and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA
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Paul Kubes
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
Correspondence to Paul Kubes: pkubes@ucalgary.ca
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Carsten Deppermann
Conceptualization
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
3
Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Rachel M. Kratofil
Formal analysis
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
Moritz Peiseler
Investigation
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
Bruna A. David
Investigation
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
Joel Zindel
Investigation
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
Fernanda Vargas E Silva Castanheira
Methodology
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
Fardau van der Wal
Formal analysis
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
Agostina Carestia
Methodology
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
4
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
Craig N. Jenne
Investigation
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
4
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
Jamey D. Marth
Conceptualization
5
Center for Nanomedicine, SBP Medical Discovery Institute, and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA
Paul Kubes
Conceptualization
1
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
Correspondence to Paul Kubes: pkubes@ucalgary.ca
J Exp Med (2020) 217 (4): e20190723.
Article history
Received:
April 22 2019
Revision Received:
October 01 2019
Accepted:
December 17 2019
Citation
Carsten Deppermann, Rachel M. Kratofil, Moritz Peiseler, Bruna A. David, Joel Zindel, Fernanda Vargas E Silva Castanheira, Fardau van der Wal, Agostina Carestia, Craig N. Jenne, Jamey D. Marth, Paul Kubes; Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets. J Exp Med 6 April 2020; 217 (4): e20190723. doi: https://doi.org/10.1084/jem.20190723
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