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-1 alpha) has been shown to have a role in the control of myeloid stem and progenitor cell proliferation. Recent evidence suggests that MIP-1 alpha 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-1 alpha on myeloid and erythroid colony formation of CD34(+) cells isolated from bone marrow and cord blood, In the presence of MIP-1 alpha, 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-1 alpha suppressed BFU-E colonies in both bone marrow and cord blood. Using thymidine suicide assays, the influence of MIP-1 alpha on the cycling status of the cells was assessed. A good correlation between the effect of MIP-1 alpha on colony formation and cell cycle progression was observed. These results suggest that there is a differential response to MIP-1 alpha when bone marrow and cord blood CD34(+) cells are compared, Using flow cytometry and a biotinylated human MIP-1 alpha/avidin fluorescein conjugate, the expression of MIP-1 alpha 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-la 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-1 alpha responsiveness observed.