Potential role of P-selectin glycoprotein ligand-1 in haematological diseases

Summary: PSGL-1 is a major counterreceptor of all three types of selectins that is expressed in several leukocyte subsets. Data presented, here prove that this mucin may be implied in haematological disorders. We established on normal peripheral blood and in samples derived from 20 AML patients that PSGL-1 is differently expressed in various leukocyte subsets. Myeloblasts appearing in acute myeloid leukaemia patients express significantly less PSGL-1 (12 000 ± 5300) than mature neutrophils (p< 0.001). In monocytic leukaemias, however, the amount of PSGL-1 on monocytic precursors is displayed in a fairly broad range which was not significantly different from that of mature monocytes (p=0.084). Monoblasts/promononocytes possess more PSGL-1 than myeloblasts and the expression pattern is completely non-overlapping. This would imply a differential expression of PSGL-1 during myeloid haemopoietic development and suggests, that the quantitation of surface PSGL-1 may help in differentiating myeloblasts from monoblasts by immunophenotyping in different AML subsets. PSGL-1 has also a certain role in the generation of procoagulant microparticles (MP) as in the PSGL-1 knockout mouse the MP number failed to increase with age and the MP contained significantly less tissue factor than wild type mice. Since PSGL-1 P-selectin interaction is crucial in generating a procoagulant effect we tested the hypothesis that the administration of a P-selectin IgG chimera (Psel-Ig) corrects bleeding tendency in a murine haemophilia model and in human haemophilic blood. The addition of Psel-Ig resulted in significant improvement of the bleeding tendency in mice and in the generation of MP in human hemophilic blood. Thus, the Psel-Ig can become an alternative route to control bleeding tendency in coagulopathies.