engleski

The role of glycans in platelet birth and death

Delayed platelet recovery and bleeding complications are major determinants of morbidity and mortality following cancer treatment. Platelets are produced by megakaryocytes (MKs), which normally reside in the vascular bone marrow (BM) niche and interact with sinusoidal BM endothelial cells to release platelets into the bloodstream. Following release, platelets circulate for 5 days in mice and 10 days in humans. The regulatory mechanisms of platelet death and birth remain unclear. In recent years it has become increasingly apparent that platelet life-span is regulated by glycan-lectin clearance mechanisms. We have now obtained direct evidence that lactosaminyl glycans (LacNAc) synthesized by the β4galatosyltransferase 1 (β4GalT1) not only regulate platelet life span, but are key regulators of thrombopoiesis. β4GalT1-/- mice exhibit severe macro-thrombocytopenia because megakaryocytes lacking functional β4GalT1 fail to produce circulating platelets, although they mature and differentiate normally. Expression of lactosaminyl glycans within hematopoietic marrow cells occurs in a stage-specific and lineage- specific fashion. Our data show that LacNAc synthesis mediated by β4GalT1 is crucial for platelet genesis but not for megakaryocyte maturation, pointing to a very specific role for LacNAc sythesis in the last step of megakaryocyte differentiation, i.e platelet production, and in the interaction with the components of the vascular BM niche.

glycans, platelets

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