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.

中文翻译：

---

巨噬细胞半乳糖凝集素对于库普弗细胞清除老化血小板至关重要

每天，巨核细胞都会产生数十亿个血小板，这些血小板循环数天，最终被肝脏清除。然而，确切的去除机制仍不清楚。唾液酸残基的丧失被认为是血小板老化和清除的特征。使用最先进的转盘活体显微镜来描绘小鼠肝脏的不同区室和细胞，我们观察到脱唾液酸化血小板主要在库普弗细胞上快速积累，只有少数在内皮细胞上，而在肝细胞上则没有。库普弗细胞耗竭阻止了老化血小板从循环中的去除。Ashwell-Morell 受体（AMR）缺陷本身对血小板摄取影响不大。巨噬细胞半乳糖凝集素 (MGL) 与 AMR 一起介导库普弗细胞对去唾液酸化或冷藏血小板的清除。有效的清除至关重要，因为血小板老化的小鼠表现出出血表型。我们的数据证明，Kupffer 细胞的 MGL 通过与 AMR 合作，在去除去唾液酸化血小板方面发挥着重要作用，从而维持健康和功能性的血小板室。