Effect of opioid peptide methionine-enkephalin in long-term cultures of human bone marrow

Methionine enkephalin, an opioid peptide belonging to the family of neuropeptides, has been shown to function as a neurotransmitter, hormone and growth factor. The present work explored its effects in long-term culture of bone marrow cells, harvested from a patient with acute lymphoid leukemia (ALL-L3) in the second complete remission. Nine cultivation flasks were established and maintained for five weeks, with medium renewal once a week. At each re-feeding, methionine-enkephalin was added to the cultures in final concentrations 10(-8), 10(-10) or 10(-12) M, and granulocyte-macrophage progenitor cells (GM-CFU) were determined among the harvested, nonadherent cell populations. The total number of nonadherent cells was 8% to 42% higher in the treated cultures than in the control, nontreated cultures, and the GM-CFU counts were three to four times higher. Those changes, although evident, did not reach statistical significance because of the small group sizes. In 1 of 9 cultures the adherent cell layer was atypical, the cell population consisted of small cells resembling the lymphoblasts, and the cell count was 2-8 times higher than in the controls. That aberrant culture has presumably arisen from residual leukemic cells remaining in the bone marrow after chemotherapy. The findings support the idea that opioid peptides, including methionine-enkephalin, participate in regulation of hematopoiesis. Two mechanisms may have accounted for the observed effects of enkephalin on cultured bone marrow cells: an indirect action, via interleukins secreted from the stromal cells upon stimulation of the opioid receptors, or a direct action on hematopoietic precursors.