Expression of Macrophage Inflammatory Protein-1 Receptors in Human CD34+ Hematopoietic Cells and Their Modulation by Tumor Necrosis Factor- and Interferon-γ

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Abstract
Macrophage inflammatory protein-1 (MIP-1) can stimulate growth inhibitory and potent chemotactic functions in hematopoietic cells. To investigate whether the action of MIP-1 may be regulated at the cellular receptor level, we studied the expression and modulation of MIP-1 receptors on CD34+ cells isolated from normal bone marrow (NBM), umbilical cord blood (CB), and leukapheresis products (LP). Expression of MIP-1 receptors on CD34+cells was analyzed by two-color flow cytometry using a biotinylated MIP-1 molecule. The mean percentage of LP CD34+ cells expressing the MIP-1 receptors was 67.7 ± 7.2% (mean ± SEM; n = 22) as compared with 89.9 ± 2.6% (n = 10) and 74.69 ± 7.04% (n = 10) in CB and NBM, respectively (P = .4). The expression of the MIP-1 receptor subtypes on LP CD34+ cells was studied by indirect immunofluorescence using specific antibodies for the detection of CCR-1, CCR-4, and CCR-5. Microscopical examination revealed a characteristic staining of the cytoplasmic cell membrane for all three receptor subtypes. Detailed analysis of two LP samples showed that 65.8%, 4.4%, and 30.5% of CD34+ cells express CCR-1, CCR-4, and CCR-5, respectively. Culture of LP CD34+ cells for 24 to 36 hours in the presence of tumor necrosis factor- (TNF-) and interferon-γ (IFN-γ) resulted in a significant increase in MIP-1 receptor expression. TNF- induced MIP-1 receptor upregulation in a time- and concentration-dependent manner. Our results suggest that inhibitory cytokines produced by the bone marrow microenvironment are likely to be involved in the regulation of MIP-1 receptor expression on hematopoietic cells. © 1998 by The American Society of Hematology.

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