Resistance of human hematopoietic stem cells to a monoclonal antibody recognizing CD43.
Hematopoietic progenitor cells (HPC) interact with bone marrow stroma by adhesion molecules which are thought to be critically important to the regulation of hematopoiesis. The specific roles of individual adhesion molecules involved in these interactions remain poorly understood. A monoclonal antibody (mAb) recognizing CD43, an adhesion molecule highly expressed by HPC, induces apoptosis in CD34hiLin- marrow cells. This process operates at a single-cell level, and the initiation of apoptosis requires crosslinking of surface CD43 and the presence of cytokines. In contrast to HPC, more differentiated hematopoietic cells do not undergo apoptosis in response to the CD43-mediated stimulation. Not all progenitor cells undergo apoptosis upon stimulation of CD43. Dividing progenitor cells are most affected, whereas more primitive, quiescent cells survive anti-CD43 mAb treatment. These surviving cells: A) are enriched for cobblestone area-forming cells; B) repopulate fragments of human fetal bone implanted into CX.B-17 severe combined immunodeficiency (SCID/hu) mice; C) have a potential to differentiate in vivo to myeloid and lymphoid cells, and D) have a high proliferative potential in long-term stromal cell-free liquid culture. These data indicate tha cells with hematopoietic stem cell characteristics are relatively resistant to CD43-mediated apoptosis compared to HPC and that CD43 may function as a negative regulator of early events occurring during hematopoiesis.
Bazil
V
V
Academy of Sciences of the Czech Republic, Praha, Czech Republic.
Brandt
J E
JE
Hoffman
R
R
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017209:Apoptosis / Q000502:physiology*; D016025:Bone Transplantation; D002454:Cell Differentiation; D002455:Cell Division; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D051917:Leukosialin; D051379:Mice; D012795:Sialoglycoproteins / Q000032:analysis*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051917:Leukosialin; C465014:SPN protein, human; D012795:Sialoglycoproteins; C497863:Spn protein, mouse