RESISTANCE OF HUMAN HEMATOPOIETIC STEM-CELLS TO A MONOCLONAL-ANTIBODYRECOGNIZING 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 adhe sion molecules involved in these interactions remain poorly understood , A monoclonal antibody (mAb) recognizing CD43, an adhesion molecule h ighly expressed by HPC, induces apoptosis in CD34(hi)Lin(-) marrow cel ls, This process operates at a single-cell level, and the initiation o f 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 fr agments of human fetal bone implanted into CX.B-17 severe combined imm unodeficiency (SCID/hu) mice; C) have a potential to differentiate in vivo to myeloid and lymphoid cells, and D) have a high proliferative p otential in long-term stromal cell-free liquid culture, These data ind icate that cells with hematopoietic stem cell characteristics are rela tively resistant to CD43-mediated apoptosis compared to HPC and that C D43 may function as a negative regulator of early events occurring dur ing hematopoiesis.