A MONOCLONAL-ANTIBODY RECOGNIZING CD43 (LEUKOSIALIN) INITIATES APOPTOSIS OF HUMAN HEMATOPOIETIC PROGENITOR CELLS BUT NOT STEM-CELLS

CD43 (the major sialoglycoprotein of leukocytes) is an adhesion molecu le broadly expressed on hematopoietic cells. A monoclonal antibody rec ognizing this molecule induces apoptosis of lineage marker-negative bo ne marrow hematopoietic progenitor cells (HPCs) that express CD34 at a high density (CD34(hi) LIN(-)). However, not all cells within this po pulation undergo apoptosis on stimulation via CD43, Dividing progenito r cells are most highly affected, whereas more primitive quiescent cel ls survive anti-CD43 monoclonal antibody treatment. These surviving ce lls (1) are enriched for cobblestone area-forming cells, (2) repopulat e fragments of human fetal bone implanted into C.B-17 scid/scid mice, (3) have a potential to differentiate in vivo to myeloid and lymphoid cells, and (4) have a high proliferative potential in long-term stroma l cell-free liquid culture. These data indicate that cells with hemato poietic stem cell characteristics are relatively resistant to CD43-med iated apoptosis as compared with HPCs. Thus, CD43 may be specifically involved in the regulation of HPC proliferation. (C) 1996 by The Ameri can Society of Hematology.