Biomedical subjects

Jiale He

Publications and source records attributed to Jiale He.

6 recordsLinked to original sources

PubMed2006

Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell death.

Galectin-1 kills immature thymocytes and activated peripheral T cells by binding to glycans on T cell glycoproteins including CD7, CD45, and CD43. Although roles for CD7 and CD45 in regulating galectin-1-induced death have been described, the requirement for CD43 remains unknown. We describe a novel role for CD43 in galectin-1-induced death, and the effects of O-glycan modification on galectin-1 binding to CD43. Loss of CD43 expression reduced galectin-1 death of murine thymocytes and human T lymphoblastoid cells, indicating that CD43 is required for maximal T cell susceptibility to galectin-1. CD43, which is heavily O-glycosylated, contributes a significant fraction of galectin-1 binding sites on T cells, as T cells lacking CD43 bound approximately 50% less galectin-1 than T cells expressing CD43. Although core 2 modification of O-glycans on other glycoprotein receptors is critical for galectin-1-induced cross-linking and T cell death, galectin-1 bound to CD43 fusion proteins modified with either unbranched core 1 or branched core 2 O-glycans and expression of core 2 O-glycans did not enhance galectin-1 binding to CD43 on T cells. Moreover, galectin-1 binding clustered CD43 modified with either core 1 or core 2 O-glycans on the T cell surface. Thus, CD43 bearing either core 1 or core 2 O-glycans can positively regulate T cell susceptibility to galectin-1, identifying a novel function for CD43 in controlling cell death. In addition, these studies demonstrate that different T cell glycoproteins on the same cell have distinct requirements for glycan modifications that allow recognition and cross-linking by galectin-1.

Animals↗

PubMed2006

Galectin interactions with extracellular matrix and effects on cellular function.

In vivo, cells exist within a complex mixture of glycoproteins and proteoglycans termed the extracellular matrix (ECM). The components of the ECM are secreted by the cells in that site, and the ECM provides not only a physical support but also outside-in signals that regulate many cellular functions, including cell proliferation, differentiation, migration, and survival. Altering the composition of the ECM can thus significantly alter cell behavior. Many types of cells, including normal and malignant epithelial and mesenchymal cells, secrete galectin-1, a member of the galectin family of lectins, into the ECM surrounding the cells. Galectin-1 is known to regulate many of these same cellular functions (i.e., proliferation, differentiation, migration, and death), so that the presence of galectin-1 in ECM will modify the effects of ECM on cells. In this chapter, we present three types of assays that allow interrogation of the effects of galectin-1 on cell adhesion to ECM, cell migration through ECM, and cell death in ECM, using T-cell lines as a model cell type.

Animals↗

PubMed2006

Endothelial cell expression of galectin-1 induced by prostate cancer cells inhibits T-cell transendothelial migration.

A critical control point in the immune response to tumors or to pathogens is the egress of lymphocytes from blood into damaged or infected tissue. While several specific endothelial cell proteins promote lymphocyte adhesion to and migration across endothelium, little is known about endothelial cell surface proteins that negatively regulate transendothelial migration of lymphocytes. Galectin-1 is a mammalian lectin expressed by a variety of cell types, including endothelial cells, that has pleiotropic anti-inflammatory effects. Galectin-1 is known to alter T-cell cytokine production and to trigger T-cell death. We now demonstrate that galectin-1 inhibits T-cell migration across endothelial cells, identifying a novel anti-inflammatory effect of galectin-1. We observed reduced T-cell migration across endothelial cells induced to increase galectin-1 expression by exposure to prostate cancer cell conditioned medium, compared to T-cell migration across control-treated endothelial cells, and the inhibitory effect of galectin-1 on T-cell migration was reversed by specific antiserum. Decreased T-cell migration was not due to decreased adhesion to galectin-1 expressing endothelial cells, nor to death of T cells, as T cells lacking core 2 O-glycans and thus resistant to galectin-1 death displayed reduced migration across endothelial cells. Galectin-1 on the surface of extracellular matrix also reduced the ability of T cells to migrate through the matrix. T cells bound to galectin-1-coated matrix demonstrated enhanced clustering of CD43, including at the T-cell:matrix interface, compared to CD43 on T cells bound to matrix in the absence of galectin-1. As translocation of CD43 to the trailing edge is essential for polarized T-cell migration, these data indicate that galectin-1-mediated clustering of CD43 contributes to the inhibitory effect on T-cell migration. Inhibition of T-cell migration is a novel anti-inflammatory activity of galectin-1.

Cell Adhesion↗

PubMed2005

Effects of cocaine on nitric oxide production in bovine coronary artery endothelial cells.

Cocaine decreases coronary artery endothelial-dependent vasorelaxation. To explore the potential mechanisms, the present study examined the effect of cocaine on nitric oxide release in bovine coronary artery endothelial cells (BCAECs). In the absence of cocaine, basal nitric oxide release from BCAECs continued to accumulate in the medium over the period from 6 to 72 h. Cocaine significantly decreased nitric oxide release at each time point of the study. At 48-h treatment, cocaine (3-30 muM) produced a concentration-dependent decrease in nitric oxide release in BCAECs. In accordance with its inhibition of nitric oxide release, cocaine decreased endothelial nitric-oxide synthase (eNOS) protein levels in BCAECs in a concentration-dependent manner. In addition to the prolonged effect, cocaine pretreatment for 1 h significantly decreased basal and ATP-induced nitric oxide release in BCAECs. Whereas acute cocaine treatment did not affect basal levels of free intracellular calcium concentrations in BCAECs, it significantly decreased the ATP-induced elevation of intracellular calcium and increased its time lag to reach the peak. A quantitative approach by immunofluorescence microscopy revealed that cocaine significantly increased eNOS localized at the cell membrane in BCAECs. Collectively, the results suggest that cocaine inhibits nitric oxide release in BCAECs by decreasing intracellular calcium mobilization, increasing the inactive state of eNOS, and decreasing eNOS protein levels.

Adenosine Triphosphate↗

PubMed2003

Presentation of galectin-1 by extracellular matrix triggers T cell death.

Apoptotic elimination of T cells at sites of inflammation or infiltration into tumors limits an effective immune response. T cell apoptosis can be initiated by a variety of triggers, including galectin-1, a soluble, secreted lectin that binds to oligosaccharide ligands on cell surface glycoproteins, or to oligosaccharide ligands on extracellular matrix glycoproteins in tissue stroma. Although galectin-1 has no transmembrane domain and is secreted from cells that make it, it is not clear if galectin-1 functions as a soluble death trigger in vivo. We examined the ability of stromal cells secreting galectin-1 to kill T cells. Although the stromal cells synthesized abundant galectin-1, the majority of the galectin-1 remained bound to the cell surface, and stromal cell-associated galectin-1 killed bound T cells. In contrast, insufficient amounts of functional galectin-1 were released from the stromal cells into the media to kill T cells in the absence of contact with stromal cells. However, when stromal cells were grown on Matrigel, a mixture of extracellular matrix proteins, or on permeable membranes above Matrigel, secreted galectin-1 bound to Matrigel and killed T cells without stromal cell contact. Ten-fold less galectin-1 on Matrigel was sufficient to kill adherent T cells compared with soluble galectin-1. These results demonstrate that galectin-1 in extracellular matrix is able to directly kill susceptible T cells. Because increased galectin-1 deposition in tumor stroma occurs with tumor progression in various types of cancer, galectin-1 in stroma may act locally in the apoptotic elimination of infiltrating T cells during an immune response.

Animals↗

PubMed2002

The ST6Gal I sialyltransferase selectively modifies N-glycans on CD45 to negatively regulate galectin-1-induced CD45 clustering, phosphatase modulation, and T cell death.

The addition of sialic acid to T cell surface glycoproteins influences essential T cell functions such as selection in the thymus and homing in the peripheral circulation. Sialylation of glycoproteins can be regulated by expression of specific sialyltransferases that transfer sialic acid in a specific linkage to defined saccharide acceptor substrates and by expression of particular glycoproteins bearing saccharide acceptors preferentially recognized by different sialyltransferases. Addition of alpha2,6-linked sialic acid to the Galbeta1,4GlcNAc sequence, the preferred ligand for galectin-1, inhibits recognition of this saccharide ligand by galectin-1. SAalpha2,6Gal sequences, created by the ST6Gal I enzyme, are present on medullary thymocytes resistant to galectin-1-induced death but not on galectin-1-susceptible cortical thymocytes. To determine whether addition of alpha2,6-linked sialic acid to lactosamine sequences on T cell glycoproteins inhibits galectin-1 death, we expressed the ST6Gal I enzyme in a galectin-1-sensitive murine T cell line. ST6Gal I expression reduced galectin-1 binding to the cells and reduced susceptibility of the cells to galectin-1-induced cell death. Because the ST6Gal I preferentially utilizes N-glycans as acceptor substrates, we determined that N-glycans are essential for galectin-1-induced T cell death. Expression of the ST6Gal I specifically resulted in increased sialylation of N-glycans on CD45, a receptor tyrosine phosphatase that is a T cell receptor for galectin-1. ST6Gal I expression abrogated the reduction in CD45 tyrosine phosphatase activity that results from galectin-1 binding. Sialylation of CD45 by the ST6Gal I also prevented galectin-1-induced clustering of CD45 on the T cell surface, an initial step in galectin-1 cell death. Thus, regulation of glycoprotein sialylation may control susceptibility to cell death at specific points during T cell development and peripheral activation.

Animals↗