engleski

Enkephalins in hematopoesis: fragments of the enkephalin molecule and agents blocking neuropeptide degradation interfere with proliferation and differentiation of mouse and human bone marrow cells in vitro

Background and purpose: Opioid pentapeptides enkephalins have been found to interfere with hematopoiesis. The present work deals with the effects of oligeopetide fragments of the enkephalin molecule, as well as with the agents interfering with enzymatic degradation of the enkephalins (thiorphan, bestatin) on hematopoiesis in vitro. Material and methods: Clonal cultures of mouse and human bone marrow, and long-term culture of human bone marrow. Human bone marrow samples were obtained from 14 patients with acute lymphoid leukemia (ALL) or non-Hodgkin lymphoma (NHL) in remission, as a small part of the material intended for the autotransplantation. Results: N-terminal di-and tripeptide fragments of the enkephalin molecule, as well as the inhibitors of the cell-bound metallo-endopeptidase degrading the enkephalins and other neuropeptides – bestatin and thiorphan, all decreased the granulocyte-macrophage colony counts (GM-CFU) in clonal cultures of mouse bone marrow cells. In 5 of 14 ALL and NHL samples, however, thiorphan increased the GM-CFU count. An enhancement of the cell proliferation and differentiation was recorded in long-term culture of an ALL bone marrow. Conclusion: The results support the idea that the enkephalins and their degradation products participate in the regulation of hematopoiesis. The regulatory mechanism probably involves the membrane-bound metallo-endopeptidase degrading the enkephalins and related peptides. That enzyme si present on hematopoietic cells as the CD10 (CALLA) marker.

membrane metallo-endoproteinase (CD10; CALLA); enkephalins; bone marrow cells; cultured; leukemia; minimal residual disease

nije evidentirano