engleski

Opioid peptides contribute to the control of hematopoiesis, poster.

The CD10 marker of lymphoid, myeloid and stromal cells is a membrane-bound metallo-endopeptidase processing the enkephalins and related neuropeptides (EC 3.4.24.11). Therefore, fragments of the enkephalin molecule and the inhibitors of the membrane endopeptidase CD10 wuld be expected to affect hematopoiesis. That idea was explored in short-term (clonal) and long-term cultures of mouse or human bone marrow cells. Human samples were obtained from healthy donors of bone marrow allotransplants or from the patients with acute leukemia (AL) or non-Hodgkin lymphoma (NHL) in remission. N-terminal fragments of the methionine-enkephalin molecule reduced the granulocyte-macrophage (GM) colony formation in clonal cultures of mouse bone marrow cells, thus resembling the effects of the parent molecule. The inhibition was (partly) blocked by opioid antagonist naloxone. CD10-blocking agent thiorphan increased the colony counts in cultures of normal human bone marrow cells and in approximately one-half of the AL and NHL samples. The stimulatory effects predominantly occurred in the remission bone marrow samples from the patients with T-ALL, AML or high-malignancy grade NHL. The bone marrow samples from the patients with common ALL and from the patients with low malignancy-grade NHL were refractory to thiorphan. In a long-term culture of ALL bone marrow, thiorphan promoted proliferation of undifferentiated cells resembling the lymphoblasts. The results are compatible with the idea that opioid peptides and membrane-bound metalloproteinase(s) processing them participate in the control of hematopoiesis. These observations draw attention to hematopoietic side effects of metalloproteinase-inhibiting drugs.

hematopoiesis; stem cells; opioid peptides

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