The heparin binding PECAM-1 adhesion molecule is expressed by CD34+ hematopoietic precursor cells with early myeloid and B-lymphoid cell phenotypes

Abstract

The platelet-endothelial cell adhesion molecule-1 (PE-CAM-1), defined by the CD31 monoclonal antibody (MoAb), was initially described as a cell-cell adhesion molecule mediating both homotypic and heterotypic adhesion. In this report, we show that enriched CD34+ human hematopoietic progenitor cell populations, containing early myeloid, erythroid, and multipotential progenitor cells, are CD31+. Analyses of CD34+ cell lines representing early myeloid, multipotential, and pre- pre-B-lymphoid progenitors indicate that precursors of both myeloid and B-lymphoid cells express PECAM-1 at high levels. Three-color flow- cytometric analyses also show that normal human bone marrow CD31+ CD34+ subsets coexpress myeloid (CD33) or B-lymphoid (CD19, CD10) markers. Except for the monocytic cell line, U937, all CD34- cell lines tested, which represent more mature stages of the myeloid, erythroid, and lymphoid lineages, expressed substantially lower or negligible levels of PECAM-1. Western blotting studies indicated that the CD31 MoAb, JC/70A, detected molecules in the 120- to 140-kD molecular weight range on the monocytic CD34- CD33+ CD31+ cell line, U937; on the CD34+ CD31+ CD33+ CD19- multipotential/lymphomyeloid precursor cell lines, KG1 and KG1B; on the CD34+ CD31+ CD19+ CD10+ CD33- precursor pre-pre-B-cell line, MIK-ALL; and on a CD34(+)-enriched precursor cell population from normal human bone marrow. A single molecular weight species was generally observed with enriched membrane preparations, whereas two PECAM-1 molecules were present in whole-cell lysates of cell lines and the CD34+ bone marrow cell subset. Preliminary studies show that a proportion of the PECAM-1 molecules on the lymphomyeloid/multipotential progenitor cell line, KG1, and on the monocytic cell line, U937, binds to heparin-sepharose. A soluble form of PECAM-1 also binds heparin- sepharose. The high level of expression of PECAM-1 on CD34+ cells suggests that this glycoprotein may function as a heterotypic adhesion molecule, possibly mediating multipotential, myeloid, and early-B- lymphoid precursor cell interactions with stromal cells and extracellular matrix molecules via heparan sulfate proteoglycans. It may also act as a homotypic adhesion molecule by interacting with PECAM- 1 on bone marrow stromal macrophage-like cells and endothelial cells or on endothelial cells during stem/progenitor cell migration. Thus, this molecule has the potential importance of directing both lineage commitment and trafficking of early hematopoietic progenitor cells.

Performance prediction algorithm for autologous PBSC collection in adults and pediatric patients using large volume leukapheresis

“…18,20 Another possible mechanism of recruitment could be modification of HSC homing and transmigration caused by changes in their microenvironment, potentially induced by the use of heparin during LVL. [21][22][23] In pediatric patients, however, only a few studies have been conducted that show the recruitment of CD34+ cells in low weight children to be significantly higher with LVL compared with conventional volume procedures. As such, apart from the well-known influence of the preapheresis CD34+ cell count, there are still only two established factors in pediatric patients that have a major impact on the CD34+ cell yield: the patient's diagnosis and volume of blood processed.…”

The Role of Osteoblasts in the Hematopoietic Microenvironment

“…Most notably, CD34 + cells express very late activation antigen-4 (VLA-4), VLA-5, and leukocyte function-associated antigen-1 (LFA-1) receptors. ICAM-1, ICAM-3, CD44, LFA-3, and PECAM-1 are also constitutively expressed by these cells [77,78]. Receptor expression and density may also vary according to the maturational status of the CD34 + cell and may play a major role in the release of these cells into the circulation.…”

Changes in expression of the cell adhesion molecule PECAM‐1 (CD31) during differentiation of human leukemic cell lines

“…Characterization of PECAM-1 expression during early hematopoietic development (17) has shown that the protein is strongly expressed on enriched CD34+ human hematopoietic progenitor populations which contain multipotential progenitor cells, early myeloid and erythroid cells, stromal macrophages, and on CD34+ cell lines representing precursors of both the myeloid and B-lymphoid lineages. Bone marrow cells and cell lines which do not express CD34, and therefore represent more mature stages of all lineages, also demonstrated greatly reduced expression of PECAM-1 (17). The expression of PECAM-1 is then upregulated during terminal myeloid differentiation.…”

“…Watt el af. (17) speculated that PECAM-1 might play a central role in the regulation of hematopoiesis by selection of the appropriate hematopoietic microenvironments through 1) homotypic PE-CAM-1 interactions of precursor cells with stromal cells or endothelial cells, 2) heterotypic interactions with heparan sulfate proteoglycans, and 3) enhancement of adhesion through pl integrins, which are expressed on CD34+ cells.…”