Involvement of CD44 variant isoform v10 in progenitor cell adhesion and maturation.
CD44 has been described repeatedly to be involved in hematopoiesis. Here, we addressed the question of functional activity of CD44 variant isoform v10 (CD44v10) in progenitor cell maturation by in vivo and in vitro blocking studies with a monoclonal antibody and a receptor globulin. We became interested in this question by the observation that CD44v10 is expressed, although at a low level, on a subpopulation of bone marrow cells. Flow cytometry revealed that 15%-20% of hematopoietic cells in the fetal liver and 25%-35% of bone marrow cells in adult mice were CD44v10 positive. The majority of CD44v10+ cells was HSA+/J11d+ and CD43+. CD44v10 was not detected on CD4+, CD8+, IgM+, or IgD+ cells. A CD44v10 receptor globulin did not bind to hematopoietic progenitor cells, but to stromal elements. The CD44v10-CD44v10 ligand interaction had a major impact on the adhesion of progenitor cells to stromal elements. When healthy animals received repeated injections of either anti CD44v10 or the CD44v10 receptor globulin, committed progenitors were mobilized and significantly augmented numbers were recovered in the spleen and the peripheral blood. Furthermore, the CD44v10-CD44v10 ligand interaction, which had no impact on progenitor expansion, influenced progenitor maturation, particularly of the B-cell lineage. Although the nature of the CD44v10 ligand remains to be explored, the supportive role of CD44v10 in progenitor maturation and, importantly, the efficient mobilization of progenitor cells by anti-CD44v10 and a CD44v10 receptor globulin could be of clinical benefit in peripheral blood stem cell transplantation.
Rösel
M
M
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg.
Khaldoyanidi
S
S
Zawadzki
V
V
Zöller
M
M
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D015851:Interleukin-7 / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D017154:Stromal Cells / Q000166:cytology
D000911:Antibodies, Monoclonal; C117722:CD44v10 antigen; D018960:Hyaluronan Receptors; D015851:Interleukin-7; D008024:Ligands