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Supplementary Materialscells-09-01792-s001

Supplementary Materialscells-09-01792-s001. many cell models highlighting the important role of this factor in myelopoiesis, lymphopoiesis, and erythropoiesis. The human HL-60 cell line is often used as a model of myeloid cell differentiation producing neutrophil-, eosinophil-, or macrophage-like cells depending on differentiation stimuli. There is evidence that galectin-1 is readily expressed in HL-60 cells, however no changes were reported at the mRNA level in differentiated cells [23,26]. Surprisingly, we noticed a 4-fold increase of intracellular galectin-1 protein expression in neutrophil-like cells, differentiated from HL-60 cells by 1.3% dimethyl sulfoxide (DMSO) [26]. This finding highlights a discrepancy between mRNA and protein levels for galectin-1, which was also BMS-193885 noticed in an animal model of hypometabolism Mouse monoclonal to EphA1 [113] suggesting additional regulatory mechanisms of galectin transcription and translation, e.g., miRNA-dependent galectin mRNA stability [114,115]. As galectin-1 is also found at high concentration in circulation, its abundance might be essential to maintain the functional activity of neutrophils by inducing plasma membrane NADPH activity and cell degranulation as we demonstrated in previous studies [7,115,116,117]. However, these aspects of functional activity of extracellular galectin-1 can vary in a biphasic manner depending on concentration as demonstrated for granulocytic differentiation [74] and respiratory burst of neutrophils [118]. The reason for these biological variations is not clear, although the role of glycan-dependent and glycan-independent interactions was proposed [74]. Studies with other stem-like leukemia cells (U937, U937T, and NB4) also confirmed a stimulatory role of galectin-1 in a model of hypoxia-induced granulocytic differentiation [46]. In this model, however, the role of galectin-1 was essential but not sufficient for the myeloid differentiation regardless of whether the cells were treated with the recombinant galectin-1 (10 g/mL) or the cells were under hypoxic conditions inducing the expression of galectin-1. In comparison, the differentiation of human peripheral monocyte cells into tolerogenic dendritic cells was readily induced by galectin-1 used at a concentration of 1 1 g/mL [81]. Although galectin-1 seems to be one of the regulatory factors required for the myeloid differentiation pathway, its expression at protein and gene levels was not changed in classically (M1) and alternatively (M2a and M2c) activated macrophages from human monocytes [48]. Galectin-1 is also involved in the lymphopoietic processes leading to generation of mature T cells and B cells. For instance, CD4+CD25+ regulatory T cells are characterized by increasing expression of galectin-1 in a model of T-cell receptor (TCR) activation [119]. The overexpression of galectin-1 is important to maintain the functions of this T cell population as neutralizing galectin-1 antibody blocks in vitro their suppressive activity related to regulating autoimmune responses. In more general context, TCR receptor presence seems to be an essential factor for galectin-1 to modulate overall thymocyte development through transient activation of the ERK pathway [120]. In comparison, CD69 was found to be a key BMS-193885 galectin-1-binding receptor in CD4+ T cells responsible for inhibiting Th17 cell differentiation by recombinant galectin-1 (10 g/mL) since CD69-deficient cells were unresponsive [80]. Several BMS-193885 lines of evidence suggest that galectin-1 is a positive regulator or at least an associated factor in plasma cell differentiation. Indeed, treatment of the BL36 B lymphoma cell line with 5-azacytidine, which is a DNA methyltransferase inhibitor cleaning up the methylation of CpG clusters in the promoter region of galectin-1 gene [121], induced both galectin-1 protein expression and plasmatic differentiation of the cells as revealed by overexpressing a plasma cell marker CD138 [64]. Comprehensive studies with mature B cells further established that galectin-1 as well as galectin-8 are positive regulators while galectin-3 is a negative regulator of terminal B cell differentiation into plasma cells [122]. The expression of these galectins at protein levels in mature B cells was accordingly increased or decreased in response to lipopolysaccharide (LPS)-induced plasma cell differentiation [65,66]. Interestingly, a discrepancy between changes at protein and mRNA levels (mRNA decrease versus protein increase) was noticed for galectin-8 suggesting that the stability of this protein increased during differentiation. As such, both galectin-1 and -8 stimulated differentiation of B cells into immunoglobulin-producing cells through an extracellular mechanism, since recombinant galectins had a stronger binding affinity to B cells rather than to plasma cells and galectin-binding glycans inhibited the BMS-193885 plasma cell differentiation. Thus, galectin-1 and galectin-8 work in concert BMS-193885 with each other in this context, while the role of galectin-3 seems to be different facilitating the formation of memory B cell rather than plasma cells [123]. The involvement of galectin-1 in mechanisms of erythropoiesis was demonstrated in a model of.


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