Macrophage-inflammatory protein-1alpha receptor expression on normal and chronic myeloid leukemia CD34+ cells.
We have assessed expression of MIP-1alpha binding sites on the surface of CD34+ cells from normal bone marrow (NBM) and chronic myeloid leukemia (CML) peripheral blood. This study has highlighted a small subpopulation of CD34+ (15.7 +/- 6.2% in NBM and 9 +/- 4% in CML), which has specific macrophage-inflammatory protein-1alpha (MIP-1alpha) cell surface binding sites. Further phenotypic characterization of the receptor-bearing cells has shown that they do not express the Thy-1 Ag, suggesting that they are committed progenitor cells rather than CD34+ Thy+ stem cells. However, more than 80% of methanol-fixed CD34+ cells do bind MIP-1alpha, suggesting that these cells may possess a pool of internal receptors, although we were unable to induce cell surface expression by cytokine stimulation. The percentage of these CD34+, MIP-1alpha-R+ cells present in the CD34 compartment of NBM is significantly higher than in CML, implicating lack of binding sites as part of the mechanism for the loss of response to this chemokine seen in CML. Specific Ab to the MIP-1alpha receptor implicated in HIV infection, CCR5, revealed that very few CD34+ cells expressed these receptors and that expression was confined to the CD34+ Thy- progenitor population. Data presented in this work suggest that active binding sites for the stem cell growth inhibitor MIP-1alpha are not constitutively expressed on the surface of most resting primitive multipotent cells, and that these cells are not potential targets for HIV-1 infection through CCR5.
Nicholls
S E
SE
Leukemia Research Fund Cellular Development Unit, University of Manchester Institute of Science and Technology (UMIST), Manchester, United Kingdom.
Lucas
G
G
Graham
G J
GJ
Russell
N H
NH
Mottram
R
R
Whetton
A D
AD
Buckle
A M
AM
D018952:Antigens, CD34 / Q000302:isolation & purification*; D001773:Blood Cells / Q000737:chemistry; D002451:Cell Compartmentation; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006412:Hematopoietic Stem Cells / Q000737:chemistry*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000302:isolation & purification*
D018952:Antigens, CD34; C515350:CCR3 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; C080633:macrophage inflammatory protein 1alpha receptor