Biological significance of the different erythropoietic factors secreted by normal human early erythroid cells

Evidence is accumulating that autocrine/paracrine regulatory mechanisms play an important role in regulating normal hematopoiesis. To support this, various growth factors, cytokines and chemokines are expressed and secreted by normal early and differentiated hematopoietic cells. In this review, we summarize recent advances in the identification and understanding of the role of autocrine/paracrine axes in normal human erythropoiesis. We will also address a biological significance of the secretion of (i) metalloproteinases which in addition to growth factors and cytokines are secreted by normal erythroid cells and (ii) membrane-derived microvesicles (MV), that are shed from the surface of maturating erythroblasts/reticulocytes, and as we postulate may also play a role in intercellular communication. We hypothesize that all these factors together play an important role in a crosstalk between erythroid cells and their environment. A better understanding of intercellular crosstalk operating in normal erythropoiesis and of the mechanisms regulating synthesis of these endogenously produced factors may allow us to develop more efficient therapeutic strategies to treat various erythropoietic disorders.