Decreased stroma adhesion capacity of CD34+ progenitor cells from mobilized peripheral blood is not lineage- or stage-specific and is associated with low beta 1 and beta 2 integrin expression.
Molecular mechanisms leading to mobilization of hematopoietic cells from bone marrow (BM) to peripheral blood (PB) involve modulation of adhesion molecule expression on these cells that probably result in changes in adhesion capacity to the microenvironment. However, it is not clear whether these changes involve different stages or lineages of progenitor cells. In this study, we compared the capacity of mature and immature clonogenic progenitor cells from granulocyte colony-stimulating factor (G-CSF)-mobilized PB and normal BM CD34+ cells to adhere to complete marrow stroma. This functional capacity was assessed concurrently with molecular expression on CD34+ cells of integrins VLA-4 (alpha 4/beta 1), VLA-5 (alpha 5/beta 1), and LFA-1 (alpha L/beta 2) by interindividual (between mobilized PB and normal BM) and intraindividual (between mobilized PB and steady-state BM and PB in the same patient) analysis. The proportion of adherent clonogenic progenitor cells was significantly lower in PB than in BM, not only for total progenitor cells but also for mature and immature progenitor cells, and the difference was found for granulocytic and particularly for erythroid lineages. The lower adhesion capacity of PB CD34+ cells to stroma was associated with decreased expression (signal/noise MFI ratio) of integrin alpha 4, beta 1, alpha L, and beta 2 chains whereas that of alpha 5 chain did not differ from BM cells with the lowest expression level. Similar differences in integrin expression levels were also found between mobilized PB and steady-state BM CD34+ cells in the same patient except for the alpha L chain. Moreover, we demonstrated for the first time a strong positive correlation between mobilizing capacity and expression levels on mobilized CD34+ cells for the LFA-1 alpha L chain but not for VLA-4 or VLA-5. In conclusion, the decreased adhesion capacity of mobilized PB progenitor cells to stroma involves different maturation stages and different lineages. This is associated with down-regulation of integrins VLA-4 and LFA-1, but mobilizing capacity appears positively correlated with LFA-1 levels.
Laboratory of Hematology, University Hospital of Tours, France.
Alexandra
A
Carion
Jorge
J
Domenech
Olivier
O
Hérault
Lotfi
L
Benboubker
Nathalie
N
Clément
Marie-Christine
MC
Bernard
Isabelle
I
Desbois
Philippe
P
Colombat
Christian
C
Binet
D018952:Antigens, CD34; D018821:CD18 Antigens / Q000032:analysis* / Q000502:physiology; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000502:physiology; D019070:Cell Lineage; D018920:Coculture Techniques; D019337:Hematologic Neoplasms / Q000628:therapy; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1 / Q000032:analysis; D039081:Integrin alpha5beta1 / Q000032:analysis; D019012:Integrin beta1 / Q000032:analysis* / Q000502:physiology; D007937:Leukapheresis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D017154:Stromal Cells / Q000166:cytology*
D018952:Antigens, CD34; D018821:CD18 Antigens; D039041:Integrin alpha4beta1; D039081:Integrin alpha5beta1; D019012:Integrin beta1; D016169:Lymphocyte Function-Associated Antigen-1