engleski

Enkephalins, enkephalin fragments and enkephalinase (CD10/CALLA) inhibitors affect hematopoiesis in vitro

Since the CD10 marker of lymphoid, myeloid and stromal cells functions as a membrane-bound enzyme processing the enkephalins and related neuropeptides (EC 3.4.24.11), enkephalins and their degradation products were supposed to participate in regulation of hematopoiesis. Here we describe the effects of di- and tripeptide fragments of the enkephalin molecule, as well as of the enkephalinase-inhibiting agents thiorphan and bestatin. The agents were tested in clonal and long-term cultures of mouse or human bone marrow cells. Human samples were donated by fully informed healthy volunteers or by patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) in complete remission. N-terminal fragments of the enkephalin reduced the granulocyte-macrophage (GM) colony formation of mouse bone marrow cells like the parent molecule. Thiorphan and bestatin were suppressive as well. However, thiorphan increased the colony counts in cultures of normal human bone marrow cells and in approximately one-half of the ALL and NHL samples. In a long-term culture of ALL bone marrow, thiorphan promoted cell proliferation and maturation. Thus, enkephalins and the membrane-bound enzyme metalloendopeptidase (CALLA/CD10; ‘enkephalinase’) seem to participate in the regulation of hematopoiesis.

enkephalins; opioid peptides; hematopoiesis; bone marrow cell culture; CALLA/CD10; thiorphan; bestatin; immune response; secondary messengers

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