We demonstrated that adrenergic agents may affect hematopoiesis via high and low affinity al-adrenergic receptors (alpha 1-ARs) present on bone marrow cells. Here we show that the high affinity, alpha 1-AR is present on Mac1(-) B220(+)sIgM(-) (pre-B) cells. The low affinity alpha 1-AR seems to be present on Mac1(+) B220(-) cells. Noradrenaline administration in mice rescued hematopoiesis from the toxic effect of carboplatin or X-rays sublethal irradiation. The protection was reflected by higher leukocyte and platelets counts as well as by increased bone marrow granulocyte/macrophage colony-forming units (GM-CFU). At its most effective dose (3 mg/kg, s.c.), noradrenaline protected 77% of the mice injected i.v. with 200 mg/kg of carboplatin (LD 100:170 mg/kg). The contemporary administration of the alpha 1-AR antagonist prazosin brought the percent of surviving mice down to 30% indicating that alpha 1-ARs mediated most of the noradrenaline-induced hematopoietic rescue. In vitro, noradrenaline (1 mu M) rescued GM-CFU in unseparated bone marrow cells containing the adherent population expressing the high affinity alpha 1-AR. Consistently, the hematopoietic rescue was counteracted by low concentrations (0.1 nM-10 nM) of the alpha 1-antagonist prazosin. Our findings describe a novel mechanism of hematopoietic regulation and might find application in preventing the myeloablative effect of anticancer treatments.

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