Signaling and induction of enhanced cytoadhesiveness via the hematopoietic progenitor cell surface molecule CD34

Abstract

The transmembrane glycoprotein CD34 shows a highly restricted expression on a crucial subset of hematopoietic cells. We show here that engagement of particular determinants of CD34 can lead to signal transduction and to enhanced adhesiveness of CD34+ hematopoietic cells. Monoclonal antibodies (MoAbs) directed against O-sialoglycoprotease- sensitive epitopes of CD34 (QBEND10, ICH3, BI.3C5, MY10) but not MoAbs against O-sialoglycoprotease-resistant epitopes (9F2, 8G12) induce actin polymerization in KG-1a and KG-1 cells and strongly enhanced cytoadhesiveness. The capacity to induce adhesion requires cellular energy, divalent cations, and intact cytoskeleton but not de novo protein synthesis. The observed cytoadhesion seems at least in part to be caused by a concomitant activation of the beta 2 integrin cytoadhesion pathway. It can be significantly inhibited with lymphocyte function-associated antigen-1 and intercelluar adhesion molecule-1 antibodies. Protein kinase inhibition analyses suggest that the pathways initiated by engagement of the CD34 molecule with certain CD34 MoAbs involves protein tyrosine kinases but that protein kinase C is not critically involved.

Comparative adhesion of human haemopoietic cell lines to extracellular matrix components, bone marrow stromal and endothelial cultures

“…Sodium fluoride depletes cellular adenosine triphosphate (Narayanan et al, 1991), cytochalasin B paralyses the cytoskeleton by inhibiting the assembly of actin filaments and cycloheximide inhibits protein synthesis (Majdic et al, 1994). None of these manipulations had any effect on KG1a-fibronectin adhesion, suggesting that the latter is mediated by constitutively expressed and activated molecules.…”

“…However, these interactions are poorly understood. It is well documented that HPCs express cell adhesion molecules (CAMs) belonging to several molecular families (Saeland et al, 1992;Turner et al, 1995) (Table I) and that expression of these molecules may be reduced in circulating HPCs compared with their bone marrow counterparts (Majdic et al, 1994;Leavesley et al, 1994;Turner et al, 1995). Similarly, a range of potential counterreceptors or ligands for these molecules are expressed by bone marrow extracellular matrix, stromal and endothelial cells (Gordon, 1988;Clark et al, 1992).…”

Concordant expression of class II and class III CD34 epitopes on haemopoietic cells in leukapheresis and cord blood samples with CD45/CD34 dual staining

“…Studies with murine myeloid M1 leukaemia cells that express CD34 transmembrane molecules lacking their cytoplasmic domain region point toward a role for CD34 in preventing the terminal differentiation of myeloid cells (Fackler et al, 1995). Interaction of class I and II but not class III MoAbs with CD34 leads to enhanced cellular adhesion via b 2 integrins in a leukaemia cell line expressing CD34 (Majdic et al, 1994). Leukaemic blast cells can be viewed as being arrested in their maturation and the previously mentioned findings are in accordance with studies using blast cells from a heterogenous group of leukaemic patients that indicated a higher percentage of positive cells was detected by antibodies to class II and class III epitopes compared with the percentages obtained using class I MoAb (Titley et al, 1995a).…”

Critical assessment of the efficiency of CD34 and CD133 antibodies for enrichment of rabbit hematopoietic stem cells

“…It is also possible that anti-CD34 antibody or beads binding specifically to rabbit CD34 1 cells may lead to aggregation of CD34 1 cells as reported by other studies. 43,44 This may render them sensitive or vulnerable to mechanical factors or shear stress during MACS sorting 45,46 leading to relatively higher cell death.…”