Circulating Monocytes Contribute to Erythrocyte Clearance in Polycythemia Vera

Erythropoiesis is increased in polycythemia vera (PV), with proliferation of erythroid precursors, and macrophages from erythroblastic islands play a key role in this process. Circulating monocytes were shown to perform some of the macrophage's functions in normal conditions, but their participation during stress erythropoiesis, as in PV, is yet to be determined. In this study, we evaluated the monocytes from the blood of healthy donors or PV patients regarding their phenotype, involvement in the clearance of erythroid cells, and their expression of iron-related molecules. We showed that circulating monocytes from PV patients contained red blood cell-derived material, which correlated with a reduction in Sirp-ɑ expression, indicating that they play a role in erythroid cell clearance in PV. Both PV monocytes and PV erythroid cells seem to influence the increase in erythrophagocytosis. The enhanced expression of heme-oxygenase-1 and ferroportin post-phagocytosis suggests their capability for heme degradation and externalization of residual iron. Moreover, PV monocytes presented higher expression of CD169, CD163, and VCAM-1, which are involved with erythroid adhesion, and they influenced in vitro erythroid cell line differentiation, suggesting that they may interfere with erythropoiesis in PV. Our findings highlight the similarities between PV monocytes and macrophages of erythroblastic islands. These insights contribute to a deeper understanding of erythrophagocytosis and erythropoiesis in the disease, offering new perspectives for advances in the field.