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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophages (M phi) are multifunctional cells that regulate humoral and cellular immune responses. Our studies of tumor-induced M phi-mediated dysfunction used M phi subsets which were defined by their Mac-1, Mac-2, and Mac-3 surface markers. To measure the accessory activity of M phi for T cell alloreactivity, thioglycollate-elicited peritoneal M phi from normal and tumor-bearing hosts (TBH) were labeled with anti-Mac-1, -2, or -3 antibodies and separated by flow cytofluorometry. The separated Mac-1+, -2+, and -3+ M phi were called sorted M phi, while unseparated M phi were designated unsorted M phi. Both M phi types were added to mixed lymphocyte reaction (MLR) cultures at concentrations ranging from a low of 2% M phi to a high of 20% M phi. The low concentration of unsorted normal host M phi caused a 31% suppression of alloreactivity. Suppression reached 68% when high concentrations of unsorted normal host M phi were added to the MLR cultures. Unsorted TBH M phi reduced alloreactivity by 64% and 86% at low and high concentrations, respectively. When separated into subpopulations, normal host Mac-1+ M phi reduced alloreactivity by 48% and 81% when added at low and high concentrations, respectively. TBH Mac-1+ reduced alloreactivity by 31% and 59% at low and high concentrations, respectively. There were no differences in the suppression caused by normal or TBH Mac-2+ M phi, and by normal or TBH Mac-3+ M phi. Indomethacin treatment did not effect the suppression caused by Mac-1+ M phi, suggesting that proataglandin E2 was not involved. Indomethacin treatment did reduce suppression mediated by Mac-2+, -3+, and unsorted M phi. Mac-2+ M phi dramatically enhanced alloreactivity at low concentrations with normal host Mac-2+ M phi providing greater enhancement of alloreactivity than TBH Mac-2+ M phi. The division of M phi into subpopulations on the basis of Mac antigens suggested that Mac-1+ and -3+ M phi played a major role in immunosuppression in the normal host, while Mac-3+ M phi were more active in TBH immunosuppression. Because no one population of sorted TBH M phi was more suppressive than sorted normal host M phi, we suggest that tumor-induced immunosuppression may involve a network of suppressor M phi.
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PMID:Modulation of alloreactivity by Mac-1+, -2+, and -3+ macrophages from normal and tumor-bearing hosts: flow cytofluorometrically separated macrophages. 215 12

A cDNA encoding the Mac-2 antigen, a surface marker highly expressed by thioglycollate-elicited macrophages, has been cloned by immunoscreening of a lambda gt11-P388D1 expression library. The nucleotide sequence of the cDNA is identical to that of carbohydrate-binding protein 35, a galactose-specific lectin found in fibroblasts and highly homologous to a rat IgE-binding protein from basophilic leukemia cells. The in vitro synthesized Mac-2 protein displayed the expected carbohydrate- and IgE-binding properties. By pulse-chase analysis and subcellular fractionation studies, the Mac-2 protein was found in the cytosol but was also seen to accumulate in the extracellular medium. The latter finding was surprising in view of the fact that the cDNA did not encode a signal peptide or transmembrane domain. An alternatively spliced cDNA with the potential to encode a NH2 terminally extended Mac-2 protein with a stretch of hydrophobic amino acids at its NH2 terminus was also found, but it is not clear whether it is the source of the extracellular Mac-2. Possible functions for the Mac-2 protein based on its lectin- and IgE-binding properties are discussed.
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PMID:The Mac-2 antigen is a galactose-specific lectin that binds IgE. 258 31

Two monoclonal antibodies, M3/31 and M3/38, were obtained by fusion of mouse myeloma cells with rat spleen cells immunized to immunoadsorbent-purified macrophage glycoproteins. Co-precipitation experiments show that antigenic determinants recognized by these two antibodies reside on the same molecular species, termed Mac-2, Mac-2, an antigen of 32,000 Mr, is synthesized by and expressed on the surface of thioglycollate-elicited macrophages as shown by [35S]-methionine and 125I labeling. Saturation binding experiments show that thioglycollate-elicited macrophages express 1.7 X 10(5) Mac-2 sites/cell. Thioglycollate-elicited macrophages are strongly absorptive for 125I-labeled M3/38 MAb. Kidneys are also absorptive; however, evidence is presented pointing to the nonspecificity of this absorption. Lymph node and thymus are negative, whereas spleen and bone marrow are weakly absorptive, probably due to stromal cells. Nonlymphoid tissues, such as lung, liver, heart, and brain, exhibit slight or no absorbing capacity. Cell suspensions from spleen, bone marrow, thymus, and peripheral lymph node are greater than 99% Mac-2- by immunofluorescent flow cytometry. In contrast, thioglycollate-elicited macrophages are greater than 96% strongly positive for Mac-2. Only 20% of peptone-elicited cells are weakly positive, whereas resident peritoneal macrophages and other macrophage elicited by Listeria monocytogenes, Con A, or LPS are greater than 98% negative. SDS-PAGE of [35S]-methionine-labeled Mac-2 shows that thioglycollate-elicited macrophages synthesize 10- to 30-fold more Mac-2 than other peritoneal macrophage subpopulations, whereas all types of peritoneal macrophages synthesize and express on their surfaces similar amounts of the Mac-1 antigen. Mac-2 antigen is therefore induced in macrophages only in response to specific differentiative signals.
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PMID:Mac-2, a novel 32,000 Mr mouse macrophage subpopulation-specific antigen defined by monoclonal antibodies. 617 26

Blocking conditions that are optimal for the detection of surface antigens on resident peritoneal macrophages (PM phi) by flow cytometry are not ideal for elicited or activated PM phi. A blocking step of 10% goat serum can be used routinely to detect the F4/80 and Mac-1 antigens on resident PM phi. In contrast, high concentrations (33-50% each) of combined goat and mouse sera were required to reduce nonspecific binding and to improve the detection of the F4/80 antigen on PM phi elicited by thioglycollate broth (TG) or activated by maleic anhydride divinyl ether copolymer (MVE-2). However, even low concentrations of goat serum masked the expression of the Mac-2 antigen on TG and MVE-2 PM phi. Thus, within a given elicited or activated PM phi population, different blocking conditions may be necessary to detect different surface antigens optimally. In addition to blocking, the use of isotypic controls that match the monoclonal antibody isotypes was found to be necessary for the optimal detection of antigen expression on TG and MVE-2 PM phi.
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PMID:Optimizing the detection of cell surface antigens on elicited or activated mouse peritoneal macrophages. 787 43

Mac-2 antigen, a 32-kDa murine macrophage cell-surface protein expressed on thioglycollate-elicited peritoneal exudate cells at higher levels than other macrophages, is a member of the S-(soluble) galactoside-binding lectin family with homologies to carbohydrate-binding proteins of other cell types. Murine macrophage cell lines can be ordered in a linear differentiation sequence according to their expression of Mac-2 and other surface markers (Leenen et al., Differentiation 1986. 32: 157.) We show here that antigen expression in macrophage cell lines can be regulated at the level of protein secretion. WEHI-3 cells, classified as immature macrophages by virtue of their low level of surface Mac-2 expression synthesize similar amounts of the antigen as more mature J774.2 and P388.D1 cells that express high amounts of surface Mac-2, but unlike these latter cell lines WEHI-3 cells fail to secrete the protein. Exogenously added Mac-2 binds efficiently to WEHI-3 cells and putative Mac-2-binding carbohydrates are expressed equally on WEHI-3, J774.2 and P388.D1 cells as judged by binding of plant lectins of known carbohydrate-binding specificities. Mac-2 secretion and surface expression in WEHI-3 cells is not significantly enhanced by calcium ionophore A23187, a powerful stimulator of Mac-2 secretion in other cells and a moderate stimulator in J774.2 and P388.D1 cells. WEHI-3 cells provide a valuable system for studying the mechanism of intracellular transport and secretion of Mac-2, a protein that lacks a signal sequence and does not enter the classical secretory pathway.
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PMID:Control of Mac-2 surface expression on murine macrophage cell lines. 802 May 58

Mac-2, a 30-35-kDa galactose-binding protein, is synthesized at similar levels in murine peritoneal exudate macrophages whether recruited in response to an intraperitoneal pathogen Mycobacterium microti, to sterile inflammatory stimuli such as thioglycollate broth, or to concanavalin A. In elicited or activated macrophages up to 30% of Mac-2 is constitutively secreted, and secretion is stimulated markedly by calcium ionophore A23187. Only thioglycollate-elicited macrophages express cell surface Mac-2, and binding is mostly (> 80%) a result of affinity for cell surface carbohydrate structures. Mac-2 surface expression is markedly reduced upon further activation of thioglycollate-elicited macrophages with bacterial lipopolysaccharide in vitro. Polylactosamine structures are present on all macrophage populations examined as determined by binding of Lycopersicon esculentum lectin, whereas alpha-galactosyl residues detected by Griffonia simplicifolia isolectin B4 are expressed only on the thioglycollate-elicited macrophages, indicating that these residues are the major determinants responsible for Mac-2 surface expression. Chemical cross-linking experiments have identified binding of endogenous cell-surface Mac-2 to three glycoproteins of molecular masses of 92, 125, and 180 kDa containing alpha-galactosyl and polylactosamine structures on thioglycollate-elicited macrophages. The restricted cell surface distribution of Mac-2 on thioglycollate-elicited peritoneal macrophages, a population of recently recruited monocytes, suggests a role(s) in early events of macrophage infiltration and tissue fixation such as extravasion and cell-matrix interactions.
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PMID:Regulation of secretion and surface expression of Mac-2, a galactoside-binding protein of macrophages. 830 13

Galectin-3 (formerly called Mac-2 antigen) is a approximately 30 kDa carbohydrate-binding protein expressed on the surface of inflammatory macrophages and several macrophage cell lines. We have purified from lysates of the murine macrophage cell line WEHI-3 glycoproteins that bind to a galectin-3 affinity column. Several of these receptors are labelled after biotinylation of intact cells showing their location at the cell surface. N-terminal aminoacid sequencing of intact galectin-3-binding glycoproteins isolated from preparative SDS-gels or of chemically derived fragments showed several homologies with known proteins and identification was confirmed by immunoprecipitation with specific antibodies. The glycoproteins were shown to be: the alpha-subunit(CD11b) of the CD11b/CD18 integrin(Mac-1 antigen); the lysosomal membrane glycoproteins LAMPs 1 and 2 which are known in part to be expressed at cell surfaces; the Mac-3 antigen, a mouse macrophage differentiation antigen defined by the M3/84 monoclonal antibody and related immunochemically to LAMP-2; the heavy chain of CD98, a 125 kDa heterodimeric glycoprotein identified by the 4F2/RL388 monoclonal antibodies respectively on human and mouse monocytes/macrophages and on activated T cells. Further studies showed that CD11b/CD18, CD98 and Mac-3 are major surface receptors for galectin-3 on murine peritoneal macrophages elicited by thioglycollate.
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PMID:Macrophage surface glycoproteins binding to galectin-3 (Mac-2-antigen). 911 Nov 44

Galectin-3, also known as the macrophage marker Mac-2, is a member of a family of structurally related animal lectins that exhibit specificity for beta-galactosides. In order to investigate the role of galectin-3 in acute inflammation, we have compared the number of leucocytes present in the peritoneal cavity of wild type and galectin-3 null mutant mice after intraperitoneal (i.p.) injection of thioglycolate broth. At day 1 after injection, we found no difference in the recruitment of mononuclear phagocytes and granulocytes to the peritoneal cavity. However, 4 days after thioglycolate injection, galectin-3 mutant mice exhibited a significantly reduced number of recoverable granulocytes compared to wild-type animals. As mutant granulocytes did not exhibit an accelerated rate of apoptosis and their uptake by macrophages appeared to be unaffected by the mutation, the phenotype described here suggests that galectin-3 participates in an additional level of control during the resolution of acute inflammation.
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PMID:Maintenance of granulocyte numbers during acute peritonitis is defective in galectin-3-null mutant mice. 976 9

Galectin-3 is a member of a growing family of beta-galactoside-binding animal lectins. Previous studies have demonstrated a variety of biological activities for this protein in vitro, including activation of cells, modulation of cell adhesion, induction of pre-mRNA splicing, and regulation of apoptosis. To assist in fully elucidating the physiological and pathological functions of this protein, we have generated galectin-3-deficient (gal3(-/-)) mice by targeted interruption of the galectin-3 gene. Gal3(-/-) mice consistently developed fewer inflammatory cell infiltrations in the peritoneal cavities than the wild-type (gal3(+/+)) mice in response to thioglycollate broth treatment, mainly due to lower numbers of macrophages. Also, when compared to cells from gal3(+/+) mice, thioglycollate-elicited inflammatory cells from gal3(-/-) mice exhibited significantly lower levels of NF-kappaB response. In addition, dramatically different cell-spreading phenotypes were observed in cultured macrophages from the two genotypes. Whereas macrophages from gal3(+/+) mice exhibited well spread out morphology, those from gal3(-/-) mice were often spindle-shaped. Finally, we found that peritoneal macrophages from gal3(-/-) mice were more prone to undergo apoptosis than those from gal3(+/+) mice when treated with apoptotic stimuli, suggesting that expression of galectin-3 in inflammatory cells may lead to longer cell survival, thus prolonging inflammation. These results strongly support galectin-3 as a positive regulator of inflammatory responses in the peritoneal cavity.
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PMID:Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses. 1070 23

Desialylated low density lipoprotein (LDL) is rapidly taken up and accumulated by both peripheral blood monocytes and cells isolated from human arterial intima consisting predominantly of smooth muscle cells. It is shown that thioglycollate (TG)-elicited mouse macrophages and mouse peritoneal macrophages stimulated with lipopolysaccharide (LPS) show increased expression of a membrane-bound, galactose-specific lectin that could be responsible for this uptake. In LPS-stimulated macrophages accumulation of desialylated LDL is increased ca. 2.6-fold. Accumulation of acetylated LDL in the same cells is reduced, suggesting that the galactose-specific lectin might be responsible for the uptake of desialylated LDL. Transfection of cells with the mouse macrophage Gal/GalNAc-specific lectin (MMGL) increased their capacity to take up asialofetuin (ASF) and, to a smaller extent, desialylated LDL. The uptake of desialylated LDL was small, most likely due to the high k(d) of MMGL for biantennary oligosaccharides as found on LDL, and low concentration of LDL achieved in tissue culture experiments. The data suggest that the expression of galactose-specific lectins can be elevated under inflammatory conditions, and that these receptors could contribute to foam cell formation under conditions of high desialylated LDL concentration, as might be found in arterial intima.
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PMID:Role of the macrophage galactose lectin in the uptake of desialylated LDL. 1105 18


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