DIFFERENTIAL EXPRESSION OF L-SELECTIN, VLA-4, AND LFA-1 ON CD34(-MARROW AND PERIPHERAL-BLOOD DURING G-CSF-ENHANCED RECOVERY() PROGENITOR CELLS FROM BONE)

To examine mechanisms of mobilization and homing of hematopoietic prog enitor cells, coexpression of CD34 and the adhesion molecules L-select in (CD62L), VLA-4 (alpha 4 beta 1-integrin, CD49d/CD29), and LFA-1 (al pha L beta 2-integrin, CD11a/CD18) was evaluated. Samples from leukaph eresis (LP) products and bone marrow (BM) were obtained on the same da y from patients who received granulocyte colony-stimulating factor (G- CSF) after cytotoxic chemotherapy. The proportion of CD34(+) cells exp ressing L-selectin tended to be greater in LP products compared with B M. In samples from both sources, the mean fluorescence intensity of CD 34 was significantly greater on CD34(+)/L-selectin-positive cells comp ared with the CD34(+)/L-selectin-negative cell subset. Three-color imm unofluorescence showed that early CD34(+)/HLA-DR(dim) or CD34(+)/HLA-D R(-) progenitor cells were strongly positive for L-selectin, whereas L -selectin-negative cells were only found in the CD34(+)/HLA-DR(bright) subset. The mean fluorescence intensity of VLA-4 and LFA-1 was signif icantly greater on CD34(+) cells from BM compared with LP products. Mo reover, a distinct population of CD34(dim)/VLA-4(bright) and CD34(dim) /LFA-1(bright) cells was found only in samples from BM. This subset ma y be enriched for myeloid progenitor cells, since the cloning efficien cy of CD34(+) cells for CFU-GM was significantly greater in BM samples than in LP products. Binding of CD34(+) cells to endothelial cells wa s partially inhibited by a blocking antibody to beta 2-integrin. In co nclusion, L-selectin is expressed in significant amounts on more primi tive CD34(+) cells which circulate in considerable numbers in the peri pheral blood. This suggests that L-selectin plays a role in redistribu tion and homing of hematopoietic progenitor cells to the bone marrow f ollowing cytotoxic damage. Conversely, strong expression of VLA-4 and LFA-1 was mainly found on lineage-committed progenitor cells of the bo ne marrow.