Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets
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Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets. / Deppermann, Carsten; Kratofil, Rachel M; Peiseler, Moritz; David, Bruna A; Zindel, Joel; Castanheira, Fernanda Vargas E Silva; van der Wal, Fardau; Carestia, Agostina; Jenne, Craig N; Marth, Jamey D; Kubes, Paul.
In: J EXP MED, Vol. 217, No. 4, 06.04.2020.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets
AU - Deppermann, Carsten
AU - Kratofil, Rachel M
AU - Peiseler, Moritz
AU - David, Bruna A
AU - Zindel, Joel
AU - Castanheira, Fernanda Vargas E Silva
AU - van der Wal, Fardau
AU - Carestia, Agostina
AU - Jenne, Craig N
AU - Marth, Jamey D
AU - Kubes, Paul
N1 - © 2020 Crown copyright. The government of Australia, Canada, or the UK ("the Crown") owns the copyright interests of authors who are government employees. The Crown Copyright is not transferable.
PY - 2020/4/6
Y1 - 2020/4/6
N2 - 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.
AB - 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.
U2 - 10.1084/jem.20190723
DO - 10.1084/jem.20190723
M3 - SCORING: Journal article
C2 - 31978220
VL - 217
JO - J EXP MED
JF - J EXP MED
SN - 0022-1007
IS - 4
ER -
