Development of bone marrow erythroblastic islands in hypoxic rats with intact or damaged kidney tubules.

Keeping in mind the renal origin of erythropoietin (EPO), we designed our study in order to estimate the role of kidney damage in the development of bone marrow erythropoiesis in erythroblastic islands (EI). The experiment was performed comparing intact rats with untreated and gentamicin-pretreated rats (50 mg/kg/15 days) exposed to hypobaric pressure (42.55 kPa/6 h) to stimulate hypoxia. Blood samples were taken following a 2-week period. The study included an estimation of plasma EPO levels by RIA, the number of peripheral blood parameters and bone marrow EI (classes I to V/femur), the rate of erythroid differentiation into erythroblasts, and the rate of repeated participation of macrophages in new EI reconstruction. Plasma EPO increased to 52.88 mU/ml (p < 0.01) and 23.45 mU/ml at 0 h immediately following hypobaric exposure in untreated and gentamicin-treated rats, respectively, as compared to 14.25 mU/ml in intact animals. Bone marrow recovery patterns were markedly expressed in untreated hypoxic animals throughout the observed period. The rate of erythroid differentiation into erythroblasts in EI was increased (p < 0.01) while the number of maturing EI decreased (p < 0.01); increased reconstruction was observed in involuted EI. Less pronounced stimulation of erythropoiesis was observed in hypoxic gentamicin-treated rats. The direct impact of the hypoxic stimulus on the erythropoietic bone marrow tissue was considered significant for the erythropoietic response via activation of macrophages. These data support the hypothesis that EI central macrophages play an important role as local regulators of bone marrow erythropoiesis.