Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms contributing to the proliferation and differentiation of antigen-presenting cell (APC) precursors upon antigen stimulation or tissue injury are poorly understood. Herein, we report the induction of a population of dendritic cell-like cells (DLC) with potent antigen-presentation function from unfractionated spleen cells by means of repetitive allostimulation in long-term mixed leucocyte cultures (LT-MLC). Initially, only a few adherent DLC were observed. By 4-6 weeks, however, there were large numbers of DLC which survived persistently. Features of these DLC are closely related to dendritic cells (DC), including (1) dendritic, veiled or spiny-processed morphology; (2) expression of a wide array of leucocyte surface markers including DC-associated or restricted antigens: 33D1, NLDC-145, CD11c (N418), heat-stable antigen (HSA), CD44, B7-1 and B7-2; (3) ability to migrate to draining lymph nodes and white pulp area of spleen; (4) expression of high level of major histocompatability complex (MHC) class II molecules and (5) more potent mixed leucocyte reaction (MLR)-stimulating capacity than peritoneal macrophages and APC-enriched spleen cells. DLC-stimulated MLR was inhibited by monoclonal antibodies (mAbs) to B7-1, B7-2, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), leucocyte-function associated antigen-1 (LFA-1) or very-late activation antigen-4 (VLA-4) by 30-55%. When maintained for more than 2 months, the DLC did not lose their MLR-stimulating activity, but many surface markers were down-regulated except for Mac-2 and VCAM-1, which remained stable or were up-regulated, respectively. In short-term culture, the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin (IL)-2 enhanced proliferation of DLC, while tumour necrosis factor-alpha (TNF-alpha) and IL-4 did not. IL-4 suppressed not only 'spontaneous', but also GM-CSF-enhanced proliferation, suggesting that cytokines play a differential role in DLC proliferation. These results confirm that professional APC can proliferate in response to repetitive antigen stimulation, and their proliferation is differentially regulated by cytokines. A comparison study of DLC with typical DC is being carried out in our laboratory.
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PMID:Generation of dendritic cell-like antigen-presenting cells in long-term mixed leucocyte culture: phenotypic and functional studies. 920 77

A c-myc retrovirus-transformed myeloid leukemia line, MMB3.19, of C57BL/6 (B6) origin, was developed to investigate graft-versus-leukemia (GVL) activity in murine bone marrow transplantation (BMT) models. It was previously determined that both naive and leukemia-presensitized CD4+-enriched T cells are capable of mediating GVL activity to MMB3.19 challenge in both syngeneic (B6) and allogeneic (C3H.SW-->B6) strain combinations, with the latter coinciding with minimal graft-versus-host disease. In the present study, MMB3.19 and 2 other similarly derived, yet phenotypically diverse, B6 myeloid leukemia lines (MMB1.10 and MMB2.18) were investigated for potential shared tumor antigens in the syngeneic GVL model. Morphologically, all 3 tumor lines are blastic with high cytoplasmic:nuclear ratios, but MMB2.18 displays dendritic processes, whereas MMB1.10 and MMB3.19 have a more rounded appearance. Flow cytometric analysis of the 3 lines revealed constitutive surface molecule expression of Mac-1, Mac-2, F4/80, LFA-1, B7-1, B7-2, H2Kb, H2Db, and macrophage scavenger receptor, consistent with macrophage/monocyte lineages. Furthermore, each of the lines expresses H2I-Ab, but to varying degrees, with MMB2.18 cells having the lowest percentage (31.6%). In vitro 51Cr release assays using MMB3.19-primed T-cell effectors demonstrated equivalent specific lysis of all 3 leukemia-line target cells. In addition, enzyme-linked immunospot analysis of MMB3.19-primed CD4+ T cells revealed significantly increased frequencies of tumor-stimulated interleukin (IL)-2-, IL-4-, and interferon-gamma-secreting cells when restimulated with each of the 3 leukemia lines. Furthermore, when MMB3.19-primed CD4+ T cells were administered in a BMT setting, a protective GVL effect was seen in those mice challenged with MMB1.10, MMB2.18, or MMB3.19. Therefore, in vitro and in vivo experiments indicate that the 3 distinct myeloid leukemia lines share 1 or more common major histocompatibility complex class II-restricted tumor antigens that can elicit a cross-protective in vivo T-cell GVL response.
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PMID:Cross-protective murine graft-versus-leukemia responses to phenotypically distinct myeloid leukemia lines. 1107 Dec 59