Resistance of human hematopoietic stem cells to a monoclonal antibody recognizing CD43

Abstract

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 CD34hi Lin− 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 that 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. Stem Cells 1997; 15(suppl 1): 13–19

Molecular cloning of Porimin, a novel cell surface receptor mediating oncotic cell death

“…Although mucins mainly affect cell adhesion and ligand binding, several membrane mucins have also been documented to trigger cell death or inhibition of cell proliferation, such as CD43 (leukosialin, sialophorin), CD162 (PSGL-1), and CD164 (MGC24v; refs. [26][27][28][29]. Further studies on Porimin should provide more information on the relationship between this membraneassociated mucin and cell death.…”

Molecular Mechanisms Involved in CD43-mediated Apoptosis of TF-1 Cells

“…Cells attached to the MEM-59-coated plastic were released by treating with 0.25 mg/ml O-sialoglycoprotein endopeptidase (Cedarlane Laboratories, Hornby, Canada) at 37°C for 45 min. The enzyme treatment did not affect the viability of the treated cells (32,33). The released cells were then harvested by gentle pipetting and analyzed by flow cytometry (FACSort, Becton Dickinson, Franklin Lakes, NJ).…”

“…However, the cross-linking of other cell surface receptors such as major histocompatibility complex class I glycoproteins, the T cell receptor, or the B cell receptor either with a ligand or with an agonistic mAb could also induce apoptosis (40 -42). Cross-linking of sialoglycoprotein CD43, an abundant cell surface protein of most hematopoietic cells, with mAbs was reported to induce apoptosis of proliferating human hematopoietic progenitors (32)(33)(34). Although the natural ligands inducing apoptosis via CD43 are currently unknown, possible candidates might be galectins (43)(44)(45) or the sialoglycoprotein-binding soluble or membranebound lectins such as the recently described sialoadhesin (16).…”

“…Because of Apoptosis Induction; Antiapoptotic Effect of CD50 or CD99 Antibody-Immobilized, but not soluble, anti-CD43 mAb MEM-59 specifically induced apoptosis of human hematopoietic progenitors (32,33). However, these cells are available only in limited amounts, and therefore we looked for a suitable model cell line.…”

“…Similar treatment also enhanced the affinity of ␤ 1 and ␤ 2 integrins in T cells and increased homotypic aggregation of the human mast cell line HMC-1 through the activation of protein kinase C and tyrosine kinases (29 -31). In contrast, the inter-action of proliferating hematopoietic progenitors with plasticimmobilized anti-CD43 mAb MEM-59 led to their apoptosis (32)(33)(34). Interestingly, stem cells and nonproliferating progenitors were resistant to MEM-59-induced apoptosis.…”