Differential Response of CD34+ Cells Isolated from Cord Blood and Bone Marrow to MIP‐1α and the Expression of MIP‐1α Receptors on These Immature Cells

Macrophage inflammatory protein‐1 alpha (MIP‐1α) has been shown to have a role in the control of myeloid stem and progenitor cell proliferation. Recent evidence suggests that MIP‐1α also has a stimulatory effect on proliferation of mature progenitors as well as an inhibitory effect on immature progenitors in vitro. We have compared the effect of MIP‐1α on myeloid and erythroid colony formation of CD34+ cells isolated from bone marrow and cord blood. In the presence of MIP‐1α, bone marrow granulocyte‐macrophage‐colony forming cells (GM‐CFC) were inhibited over a dose range of 15 ng/ml to 500 ng/ml, and GM‐CFC from cord blood CD34+ cells were stimulated over the same dose range. MIP‐1α suppressed BFU‐E colonies in both bone marrow and cord blood. Using thymidine suicide assays, the influence of MIP‐1α on the cycling status of the cells was assessed. A good correlation between the effect of MIP‐1α on colony formation and cell cycle progression was observed. These results suggest that there is a differential response to MIP‐1α when bone marrow and cord blood CD34+ cells are compared. Using flow cytometry and a biotinylated human MIP‐1α/avidin fluorescein conjugate, the expression of MIP‐1α receptors on CD34+ cells was assessed. The data indicated that there was little quantitative difference in overall expression of receptors (82.9% versus 93%) from bone marrow or cord blood, respectively. However, when Northern blot analysis was used, mRNA for two different MIP‐1α receptors CCR1 and CCR5 could be detected in bone marrow, but only CCR1 mRNA was seen in cord blood CD34+ samples. Therefore, the expression of different receptor subtypes on CD34+ cells may be responsible for the difference in MIP‐1α responsiveness observed.