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1.
J Immunol ; 192(3): 1294-301, 2014 Feb 01.
Article in English | MEDLINE | ID: mdl-24391218

ABSTRACT

Mannan (mannose)-binding protein (MBP) is a C-type serum lectin that plays a key role in innate immunity. MBP forms large multimers (200-600 kDa) and exhibits broad specificity for mannose, N-acetylglucosamine, and fucose. MBP exhibits high affinity for unique oligosaccharides that have been isolated from human colorectal carcinoma (SW1116) cells and characterized as highly fucosylated high m.w. type 1 Lewis glycans. In this study, we first demonstrated that MBP recognizes human primary colorectal carcinoma tissues through tumor-associated MBP ligands. We performed fluorescence-based histochemistry of MBP in human colorectal carcinoma tissues and showed that MBP clearly stained cancer mucosae in a Ca(2+)-dependent manner. Coincubation with plant (Aleuria aurantia) lectin, but not Con A, blocked MBP staining, indicating that fucose, rather than mannose, is involved in this interaction. The expression of MBP ligands was detected in 127 of 330 patients (38.5%), whereas, most significantly, there was no expression in 69 nonmalignant tissues. The MBP-staining pattern in cancer mucosae significantly overlapped with that of Lewis b [Fucα1-2Galß1-3(Fucα1-4)GlcNAc] staining, but the Lewis b staining in normal tissues was not associated with MBP staining. In addition, the MBP staining correlated inversely with the expression of CA19-9 Ag, and MBP stained 11 of 25 (44%) CA19-9 (sialyl Lewis a [NeuAc(α2-3)Galß1-3(Fucα1-4)GlcNAc])(-) colorectal carcinoma tissues. We found a favorable prognosis in patients with MBP ligand(+) tumors. These results suggest that selective recognition of cancer cells by endogenous MBP seems to be associated with an antitumor effect and that tissue staining with MBP in combination with CA19-9 may serve as a novel indicator of colorectal carcinoma tissues.


Subject(s)
Adenocarcinoma, Mucinous/chemistry , Adenocarcinoma/chemistry , Antigens, Neoplasm/analysis , Colorectal Neoplasms/chemistry , Mannose-Binding Lectin/physiology , Oligosaccharides/analysis , Adenocarcinoma/diagnosis , Adenocarcinoma/mortality , Adenocarcinoma, Mucinous/diagnosis , Adenocarcinoma, Mucinous/mortality , Adult , Aged , Aged, 80 and over , CA-19-9 Antigen/analysis , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/mortality , Epithelium/chemistry , Fluorescent Antibody Technique, Indirect , HLA-DR Antigens/analysis , Humans , Intestinal Mucosa/chemistry , Lewis Blood Group Antigens , Ligands , Lymphocytes, Tumor-Infiltrating/chemistry , Middle Aged , Neoplasm Metastasis , Predictive Value of Tests , Proportional Hazards Models
2.
J Leukoc Biol ; 81(4): 1002-11, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17242371

ABSTRACT

Jacalin, an alpha-O-glycoside of the disaccharide Thomsen-Friedenreich antigen (galactose beta1-3 N-acetylgalactosamine, T-antigen)-specific lectin from jackfruit seeds, has been shown to induce mitogenic responses and to block infection by HIV-1 in CD4+ T lymphocytes. The molecular mechanism underlying Jacalin-induced T cell activation has not been elucidated completely yet. In the present study, protein tyrosine phosphatase (PTPase) CD45 was isolated from a Jurkat T cell membrane fraction as a major receptor for Jacalin through affinity chromatography and mass spectrometry. CD45, which is highly glycosylated and expressed exclusively on the surface of lymphocytes, is a key regulator of lymphocyte signaling, playing a pivotal role in activation and development. We found that the lectin induced significant IL-2 production by a CD45-positive Jurkat T cell line (JE6.1) and primary T cells. However, this effect did not occur in a CD45-negative Jurkat T cell line (J45.01) and was blocked completely by a specific CD45 PTPase inhibitor in Jurkat T (JE6.1) and primary T cells. Furthermore, we also observed that Jacalin caused a marked increase in IL-2 secretion in response to TCR ligation and CD28 costimulation and contributed to Th1/Th2 cytokine production by activating CD45. Jacalin increased CD45 tyrosine phosphatase activity, which resulted in activation of the ERK1/2 and p38 MAPK cascades. Based on these findings, we propose a new, immunoregulatory model for Jacalin, wherein glycosylation-dependent interactions of Jacalin with CD45 on T cells elevate TCR-mediated signaling, which thereby up-regulate T cell activation thresholds and Th1/Th2 cytokine secretion.


Subject(s)
Cytokines/metabolism , Leukocyte Common Antigens/metabolism , Lymphocyte Activation , Plant Lectins/metabolism , Receptors, Mitogen/isolation & purification , Receptors, Mitogen/metabolism , T-Lymphocytes/immunology , Clone Cells , Dose-Response Relationship, Drug , Glycosylation , Humans , Interleukin-2/metabolism , Jurkat Cells , Mitogen-Activated Protein Kinase Kinases/metabolism , Plant Lectins/pharmacology , Receptors, Antigen, T-Cell/metabolism , Signal Transduction , T-Lymphocytes/metabolism
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