engleski

A model of Met-enkephalin induced alterations of the bone marrow cell proliferation

Background and purpose: The aim of the study was to define and model the suppressive effects of the opioid peptide Met-enkephalin on the bone marrow cell proliferation. Material and methods: The bone marrow cell proliferation was investigated using an in vitro assay for the granulocyte-macrophage colony-forming units (GM-CFU). The GM-CFU count at a given peptide concentration (X_n) was defined by a simple population model: X_n+1 = X_n a(1-X_n) with a=growth parameter; 0<X_n<1. The value of X_n was X_n = Z_n/Z_max, with Z_n = number of GM-CFU at peptide concentration step n (M), Z_max = mean control Z + 2SEM. The concentrations were expressed as –logM. Results: We observed no differences between simulated and experimental values (p > 0.05, t-test; correlation p < 0.05). The dose-response pattern showed circadian variations, depending on the time of the bone marrow cell collection. The inhibitory and the stimulatory effects of the Met-enkephalin on the GM-CFU counts showed chaotic oscillations during the light period, which is the resting period for mice (a = 3.67 at 10 AM and a = 3.80 at 2 PM). Periodic changes of the inhibitory and stimulatory effects of Met-enkephalin were observed during darknwess, which is the period of mouse activity (a = 2.90 with one stable oscillatory point 0.66 at 6 PM and a = 3.33 with two stable oscillatory points 0.48 and 0.83 at 6 AM). The mean value of the Met-enkephalin concentration step defining the change from the inhibitory to the stimulatory effect on the GM-CFU count, and vice versa, was –logM = 2.125. The same population model holds for the absolute number of GM-CFU, as defined by the equation Z_n+1 = Z_n a-a(Z_nČ2/Z_max). The number of the GM-CFU in the accessory cell depleted bone marrow exhibited significant negative correlation to the growth parameter a (r = -0.962, p<0.05) which was not observed in complete bone marrow. Conclusion: The presented model permits analysis of the dynamics of the growth responses to the petide concentratiob with respect to the time/circadian changes of the bone marrow cellular proliferative activity.

Cell growth; chaotic; periodic; model; population; bone marrow; Met-enkephalin; opioid peptides; hematopoiesis; circadian clock

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