engleski

Participation of opioid peptides in the control of hematopoiesis

Introduction: Previous work showed inhibitory effects of opioid pentapeptides enkephalins on cultured mouse bone marrow cells (Boranić et al., Reg Immunol 6:421,1994). Since the CD10 marker of lymphoid, myeloid and stromal cells functions as a membrane-bound enzyme processing the neuropeptides (EC 3.4.24.11, 'enkephalinase'), enkephalins and related peptides 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. Materials and Methods: The agents were tested in clonal and long-term cultures of mouse and human bone marrow cells. Human samples were donated by healthy volunteers or by patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) in complete remission. The samples constituted small parts (1-2%) of the material collected and stored for allo- or autografting, respectively. Results: In clonal cultures of mouse bone marrow cells, N-terminal fragments of the enkephalin reduced the granulocyte-macrophage (GM) colony formation, like the parent molecule. Thiorphan and bestatin were suppressive as well. Opioid antagonist naloxone blocked (partly) the inhibition by the enkephalin fragments. 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 proliferation of cells resembling the lymphoblasts. Conclusion: The observations indicate a combination of specific (opioid receptor-mediated) and nonspecific actions of tested agents on hematopoiesis. Findings in the ALL and NHL bone marrow samples open the possibility that malignant cells respond to putative neuroendocrine regulatory mechanisms affecting the hematopoiesis.

hematopoiesis; growth factors; opioid peptides

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