Endoglycan, a Member of the CD34 Family of Sialomucins, Is a Ligand for the Vascular Selectins

Abstract

The interactions of the selectin family of adhesion molecules with their ligands are essential for the initial rolling stage of leukocyte trafficking. Under inflammatory conditions, the vascular selectins, E- and P-selectin, are expressed on activated vessels and interact with carbohydrate-based ligands on the leukocyte surface. While several ligands have been characterized on human T cells, monocytes and neutrophils, there is limited information concerning ligands on B cells. Endoglycan (EG) together with CD34 and podocalyxin comprise the CD34 family of sialomucins. We found that EG, previously implicated as an L-selectin ligand on endothelial cells, was present on human B cells, T cells and peripheral blood monocytes. Upon activation of B cells, EG increased with a concurrent decrease in PSGL-1. Expression of EG on T cells remained constant under the same conditions. We further found that native EG from several sources (a B cell line, a monocyte line and human tonsils) was reactive with HECA-452, a mAb that recognizes sialyl Lewis X and related structures. Moreover, immunopurified EG from these sources was able to bind to P-selectin and where tested E-selectin. This interaction was divalent cation-dependent and required sialylation of EG. Finally, an EG construct supported slow rolling of E- and P-selectin bearing cells in a sialic acid and fucose dependent manner, and the introduction of intact EG into a B cell line facilitated rolling interactions on a P-selectin substratum. These in vitro findings indicate that EG can function as a ligand for the vascular selectins.

Podocalyxin-Targeting Comparative Glycan Profiling Reveals Difference between Human Embryonic Stem Cells and Embryonal Carcinoma Cells

“…It is also noted that the signal intensities of a series of O-glycan-binders, e.g., Jacalin, WFA, ACA, MPA, VVA and SBA, were evidently increased in both cells. These results are consistent with the previous observation that podocalyxin is a heavily glycosylated sialomucin [5,7]. Interestingly to note, among α2-6Sia-binders (SNA, SSA and TJA-I), the signals of only SNA showed decrease by the sialidase treatment, whereas other α2-6Sia-binders did not.…”

“…Since the podocalyxin gene was highly expressed in both hESCs and hECCs, the difference between these cells is attributed to significant change in glycan structures of podocalyxin. Although the theoretical molecular mass of podocalyxin is merely 55 kDa, actually immunoprecipitated podocalyxin was found to be >200 kDa, probably with heavily glycosylation consistent with previous reports that the molecular mass of podocalyxin is extremely large representing a feature of sialomucin [5,7]. In our previous works using lectin microarray, we successfully categorized murine and human somatic stem cells into groups based on differentiation potencies [43,44].…”

“…Podocalyxin is a member of the CD-34-related family of sialomucins [3][4][5][6][7][8]. Podocalyxin was originally cloned from the human kidney as a component of the podocyte cell glycocalyx, while it was also identified on vascular endothelium and hematopoietic cells [3,4,[9][10][11].…”

Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism

“…E-selectin expression) levels. However, E-selectin has other known binding ligands that may participate in this process including P-selectin glycoprotein ligand-1 (PSGL-1), endoglycan, lysosome-associated membrane protein (LAMP)-1, LAMP-2 and CD44 among others [35], [36], [37], [38], [39], [40], [41]. Further analysis of these ligands may reveal their involvement in the observed adhesion.…”

Aberrant expression of selectin E, CXCL1, and CXCL13 in chronic endometritis

“…VCAM-1 contributes to tethering/rolling of integrin a4b7À memory B cells by interaction with very late antigen-4 on B cells, whereas selectin E binds to endoglycan, a sialomucin presented on circulating B cells. 11,12 Selectin P expression is confined to Weibel-Palade bodies in resting endothelial cells and is relocated on the cell surface rapidly after activation serving as another ligand to endoglycan. In addition, circulating B cells show selective migratory responses to the specific chemokines such as CCL-2, -19, -21, CXCL-1, -8, -12, and -13, which are the ligands for CCR-2, -7, CXCR-1, -2, -4, or -5.…”