E-selectin and very late activation antigen-4 mediate adhesion of hematopoietic progenitor cells to bone marrow endothelium

Abstract

Adhesion of CD34+ hematopoietic progenitor cells (HPCs) to sinusoidal endothelium probably plays a key role in homing of transplanted CD34+ HPCs to the bone marrow (BM). We have investigated the role of various adhesion molecules in the interaction of purified CD34+ HPCs derived from BM or peripheral blood (PB) and a human BM-derived endothelial cell line. Adhesion of CD34+ HPCs to endothelial cells was measured with the use of a double-color flow microfluorimetric adhesion assay. In this assay, adhesion is measured under stirring conditions, simulating blood flow in sinusoidal marrow vessels. Adhesion of PB CD34+ cells to human BM endothelial cells (HBMECs) was observed only after interleukin (IL)-1beta prestimulation of the endothelial cells. This adhesion was strongly increased after addition of phorbol-myristate acetate (PMA). Adhesion of PB CD34+ cells to IL-1beta-prestimulated HBMECs was inhibited by blocking monoclonal antibodies (mAbs) against E-selectin and by neuraminidase treatment of the PB CD34+ cells. mAbs against very late activation antigen (VLA)-4 inhibited adhesion only when the E-selectin-mediated interaction was prevented. No clear inhibiting effect was found with blocking mAbs against beta2-integrins. Stimulation with the beta1-integrin-activating mAb, 8A2, induced adhesion of CD34+ cells to endothelial cells. In conclusion, stimulation of both endothelial cells and CD34+ HPCs is necessary for adhesion of CD34+ HPCs to endothelial cells. We furthermore demonstrated that E-selectin and VLA-4 mediated this adhesion.

Migration of Human Hematopoietic Progenitor Cells Across Bone Marrow Endothelium Is Regulated by Vascular Endothelial Cadherin

“…It was previously shown by our group and others that the ␤1 integrins very late Ag (VLA)-4 and VLA-5 are required for efficient transendothelial migration of CD34 ϩ cells (2,11,41,42). Therefore, we investigated which adhesion molecules that are known ligands for VLA-4 and VLA-5 mediate the migration of CD34 ϩ cells across HBMECs.…”

Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking

“…In fact, BM microvessels express E-selectin constitutively, while E-selectin is inducible on endothelial linings of inflamed tissues and of bronchial mucosa, a common PCa target tissue (7)(8)(9). Mechanistically, an identical traffic control axis involving selectins is well-known in the extravasation of hematopoietic progenitor cells (HPC) into BM (10,11). HPC rolling on E-and platelet (P)-selectin is regulated by sLe X -bearing glycoforms of CD44 (HCELL), PSGL-1 and glycolipids (10,12,13).…”

Murine neuronal progenitor cells are preferentially recruited to tumor vasculature via a4-integrin and SDF-1a dependent mechanisms

“…2B), however, C17.2-luc cell recruitment to activated normal endothelium was blocked completely by function blocking antibodies to α 4 -integrin, suggesting that VLA-4 is the critical receptor for C17.2-luc cell recruitment to inflamed endothelium, consistent with its role in recruitment of hematopoietic progenitors to bone marrow endothelium. 10 Function blocking antibodies to any of the adhesion molecules examined, did not, however, have any effect on C17.2-luc cell recruitment to tumor endothelium (Fig. 4), suggesting the presence of additional adhesive mechanisms.…”

“…Neural cells have been demonstrated to express CD34, 27 commonly associated with hematopoietic stem cells and endothelial cells, and recent DNA microarray analysis has confirmed that neuronal precursors express Ephrin B2 and neuropilin, whereas glial precursors express CD44 and CXCR4, the receptor for the CXC chemokine, SDF-1. 28 The recruitment of hematopoietic progenitor cells has been shown previously to be mediated via selectins, [8][9][10][11]12 and VLA-4, 10,11 and recently it was demonstrated that recruitment of embryonic progenitors to tumor vessels was mediated via E-and P-selectins and PSGL-1. 29 Similarly SDF-1 is known to be chemotactic for CD34+ progenitors, 21,30 however, to date, no studies have dissected the specific molecules that mediate neuronal progenitor recruitment to underlying vasculature.…”

“…Previously it has been reported that hematopoietic progenitor cells can be recruited to vascular beds via a combination of selectins, [8][9][10][11] CD44 8,12 and very late antigen (VLA)-4. 10,11 As cells recruited from the circulation must first interact with the underlying vasculature, we decided to examine the recruitment of progenitor cells to normal or tumor-derived endothelium (TEC) in an in vitro model of microvasculature. The molecular mechanisms identified in this manuscript could be exploited to improve the delivery of neuronal progenitors in vivo and potentially enhance the effects of progenitor based cell therapies.…”