Роль тканевого эритропоэтина и механизмов обратной связи в локальной регуляции эритропоэза

Abstract

Erythroblastic islets (EI) of rat bone marrow were cultured for 24, 48, or 72 h together with various erythrocytes, simulating the state of erythron hyper- or hyporegeneration in the in vitro system. The concentration of erythropoietin was determined in the control and experimental cultures of EI by two-site enzyme-linked immunosorbent assay. With the addition of reticulocytes/young red blood cells (erythron hyperregeneration model) at a dose of 30 or 60 cells / 1 EI, after 24 h of cultivation, the concentration of erythropoietin in the culture medium increased by 37% compared to control cultures. In cultures with 120/1 EI reticulocytes / young red blood cells, the concentration of erythropoietin decreased by 25% by 48 h. The addition of mature/old red blood cells (an erythron hyporegeneration model) caused inhibition of erythropoietin synthesis in EI culture. By 48 h, the content of this hormone in the cultivation medium significantly decreased in all series of the experiment: in cultures with 30 cells / 1 EI - by 18%, and in cultures with a large erythrocyte load - by 28%. In 72-h cultures containing 30, 60, or 120 red blood cells / 1 EI, the concentration of erythropoietin decreased by 26%, 40%, and 53%, respectively, compared with the control. We found that local regulation of erythropoiesis is directly related to the synthesis of erythropoietin in EI and depends on the number and maturity of cells produced by red bone marrow. The data obtained suggest that it is tissue erythropoietin that is the most important link in the implementation of feedback mechanisms that provide an adequate response of the erythron to an oxygen demand in physiological conditions and support erythropoiesis in pathological conditions accompanied by small production of erythropoietin in the kidneys.