Erythroid Stress Research Articles

In vitro growth of sheep erythroid progenitors.

We have attempted to define culture conditions suitable to support the in vitro growth of early erythroid progenitors (BFU-E), derived from the liver or bone marrow and blood of fetal and adult sheep. Testing a wide variety of conditions showed that only some batches of fetal lamb sera made a notable difference to growth. BFU-E from normal fetal blood were demonstrated sporadically: they appeared regularly in low numbers in blood taken during erythroid (anaemic) stress. Adult blood only contained sporadic BFU-E during severe anaemic stress. This difficulty in demonstrating circulating BFU-E in sheep may be due to a genuine paucity of such cells or to an undefined requirement for in vitro growth.

Abnormal membrane surface properties during maturation of rat reticulocytes elicited by bleeding as measured by partition in two-polymer aqueous phases.

Partition of cells in two-polymer aqueous phases is an extremely sensitive method for the separation of cells and for tracing subtle changes in the cells' membrane surface properties (primarily surface charge) as a function of in vivo processes (e.g. differentiation, maturation, ageing). Combining isotope labelling and cell countercurrent distribution techniques we have examined the membrane surface properties of rat reticulocytes produced in response to erythroid stress by bleeding. It was found that the rapid increase in the partition coefficient of normal reticulocytes subsequent to release into the peripheral blood (which reflects a rapid increase in membrane surface charge) is absent in reticulocytes produced in response to bleeding. In this way the reticulocytes behave like those produced in response to repeated phenylhydrazine injections. 'Stress reticulocytes' never mature to erythrocytes having normal membrane surface properties as judged by partition. The experiments show that our previous results are not due to the phenylhydrazine per se but rather to the production of 'stress reticulocytes'. Further, if remodelling of the phlebotomy-induced reticulocyte cell membrane occurs in the circulation as has been suggested it does not lead to a cell with normal membrane surface properties. Whether the abnormal membrane surface properties of 'stress reticulocytes' and of the erythrocytes to which they give rise affect the cells' life-span is not clear since phenylhydrazine-induced 'stress reticulocytes' have been reported to have at least a component of short-lived cells while the phlebotomy-induced cells are said to have a virtually normal life-span. It is likely that reticulocytes produced in severe anaemias, in general, mature to erythrocytes having abnormal surface properties (i.e. lower membrane surface charge).

Surface remodelling of reticulocytes produced in response to erythroid stress.

ACCELERATED erythropoiesis is associated with the production of reticulocytes of excessive size, perhaps as the result of skipped divisions during erythroid cell proliferation in the bone marrow1. Isotopic studies have been interpreted as showing that these “stress reticulocytes” are short-lived and are replaced by progressively smaller cells with more normal life spans1–6. It has recently been suggested, however, that stress reticulocytes are not destroyed in toto but are made smaller by a process of remodelling or surface fragmentation7; loss of only portions of these cells could explain most of the isotopic findings, although the residual cells might remain intact.