The fibrinolytic system of human bone marrow
The fibrinolytic system of normal and leukaemic bone marrow was examined. Normal bone marrow had a very active fibrinolytic system due to abundant free t-PA, with negligible contribution from u-PA. High levels of PAI-2 antigen were observed in addition to PAI-1. Plasminogen, the precursor of plasmin was detected, mainly in complex with α2-AP, indicating that plasmin had been generated. The balance of the fibrinolytic system in normal bone marrow contrasted with the system in plasma, where plasmin is not normally generated. In bone marrow the t-PA level was greater than that of the inhibitors while in plasma t-PA circulates in complex with PAI-1. t-PA, u-PA, u-PAR, PAI-1 and PAI-2 were localised to cells of the myeloid, monocytic, megakaryocytic and T-lymphoid lineages in normal marrow. In contrast, cells of the B-lymphoid lineage did not possess the antigens of interest. In addition, non-haematopoietic cells in the marrow were examined, and it was observed that osteocytes, endothelial cells, smooth muscle cells and adipocytes contained the antigens of the fibrinolytic system. PAI-1, PAI-2, u-PA, u-PAR and probably t-PA were synthesised by the cells of the marrow, while plasminogen and α2-AP arose from the general circulation. The activity and antigen levels of the components of the fibrinolytic system differed between normal and leukaemic bone marrow. In leukaemic marrow, u-PA was observed, while t-PA and PAI-2 were decreased compared with normal bone marrow. PAI-1, plasminogen, α2-AP and plasmin-α2-AP complex were similar to normal bone marrow. The appearance of u-PA was probably associated with the malignant phenotype and may confer an invasive advantage on the leukaemic cell. In addition, the profile of the fibrinolytic system observed in leukaemic bone marrow may contribute to the haemorrhagic symptoms associated with certain forms of leukaemia.