Differential expression of L-selectin, VLA-4, and LFA-1 on CD34+ progenitor cells from bone marrow and peripheral blood during G-CSF-enhanced recovery.
To examine mechanisms of mobilization and homing of hematopoietic progenitor cells, coexpression of CD34 and the adhesion molecules L-selectin (CD62L), VLA-4 (alpha 4 beta 1-integrin, CD49d/CD29), and LFA-1 (alpha L beta 2-integrin, CD11a/CD18) was evaluated. Samples from leukapheresis (LP) products and bone marrow (BM) were obtained on the same day from patients who received granulocyte colony-stimulating factor (G-CSF) after cytotoxic chemotherapy. The proportion of CD34+ cells expressing L-selectin tended to be greater in LP products compared with BM. In samples from both sources, the mean fluorescence intensity of CD34 was significantly greater on CD34+/L-selectin-positive cells compared with the CD34+/L-selectin-negative cell subset. Three-color immunofluorescence showed that early CD34+/HLA-DRdim or CD34+/HLA-DR- progenitor cells were strongly positive for L-selectin, whereas L-selectin-negative cells were only found in the CD34+HLA-DRbright subset. The mean fluoresence intensity of VLA-4 and LFA-1 was significantly greater on CD34+ cells from BM compared with LP products. Moreover, a distinct population of CD34dim/VLA-4bright and CD34dim/LFA-1bright cells was found only in samples from BM. This subset may be enriched for myeloid progenitor cells, since the cloning efficiency of CD34+ cells for CFU-GM was significantly greater in BM samples than in LP products. Binding of CD34+ cells to endothelial cells was partially inhibited by a blocking antibody to beta 2-integrin. In conclusion, L-selectin is expressed in significant amounts on more primitive CD34+ cells which circulate in considerable numbers in the peripheral blood. This suggests that L-selectin plays a role in redistribution and homing of hematopoietic progenitor cells to the bone marrow following cytotoxic damage. Conversely, strong expression of VLA-4 and LFA-1 was mainly found on lineage-committed progenitor cells of the bone marrow.
Department of Internal Medicine V, University of Heidelberg, Germany.
R
R
Möhle
S
S
Murea
M
M
Kirsch
R
R
Haas
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006684:HLA-DR Antigens / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000737:chemistry*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis*; D019041:L-Selectin / Q000032:analysis*; D007937:Leukapheresis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis*; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000473:pathology / Q000628:therapy; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000628:therapy; D016201:Receptors, Lymphocyte Homing / Q000032:analysis*
D018952:Antigens, CD34; D006684:HLA-DR Antigens; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D016179:Granulocyte Colony-Stimulating Factor