Galectin-1 induces 12/15-lipoxygenase expression in murine macrophages and favors their conversion toward a pro-resolving phenotype

Rostoker, Ran; Yaseen, Hiba; Schif-Zuck, Sagie; Lichtenstein, Rachel G.; Rabinovich, Gabriel A.; Ariel, Amiram

doi:10.1016/j.prostaglandins.2013.08.001

Cited by 44 publications

(49 citation statements)

References 60 publications

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“…The immunosuppressive role of Gal-1 was further supported by studies with Tregs where cells from Gal-1 null mice exhibited reduced regulatory activity (10). More recent studies emphasized the immunosuppressive effect of Gal-1 in macrophages and cells of the microglia compartment, which showed a shift toward an M2 phenotype and reduced secretion of proinflammatory cytokines upon exposure to this lectin (11).…”

mentioning

confidence: 90%

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Greenberg

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1–expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan– and dose-dependent. At concentrations ≤0.25 µM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1–induced migration. Exposure to concentrations ≥1 µM resulted in ERK(1/2)-dependent apoptosis and disruption of the F-actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1–deficient mice exhibited increased recruitment of eosinophils and CD3+ T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis.

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confidence: 90%

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Greenberg

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Rostoker et al recently showed that Gal-1 was selectively expressed in CD11b high macrophages, and its expression declined significantly once these cells converted toward a CD11b low phenotype [49]. Moreover, CD11b low macrophages are the predominant subtype to depart the peritoneum [49].…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, CD11b low macrophages are the predominant subtype to depart the peritoneum [49]. To determine whether VitC regulated reprogramming of peritoneal macrophages to proresolution CD11b low phenotype we used flow cytometry to examine the distribution of CD11b high and CD11b low population on macrophages isolated on day 3 and day 5 following TG-induced peritonitis in VitC sufficient or deficient mice.…”

Section: Resultsmentioning

confidence: 99%

Resolution of Sterile Inflammation: Role for Vitamin C

Mohammed

Fisher

Huynh

et al. 2014

Mediators of Inflammation

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Introduction. Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC) attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited. Methods. To examine whether physiological levels of VitC modulate resolution of inflammation, we used transgenic mice lacking L-gulono-γ-lactone oxidase. VitC sufficient/deficient mice were subjected to a thioglycollate-elicited peritonitis model of sterile inflammation. Some VitC deficient mice received daily parenteral VitC (200 mg/kg) for 3 or 5 days following thioglycollate infusion. Peritoneal macrophages harvested on day 3 or day 5 were examined for intracellular VitC levels, pro- and anti-inflammatory protein and lipid mediators, mitochondrial function, and response to lipopolysaccharide (LPS). The THP-1 cell line was used to determine the modulatory activities of VitC in activated human macrophages. Results. VitC deficiency significantly delayed resolution of inflammation and generated an exaggerated proinflammatory response to in vitro LPS stimulation. VitC sufficiency and in vivo VitC supplementation restored macrophage phenotype and function in VitC deficient mice. VitC loading of THP-1 macrophages attenuated LPS-induced proinflammatory responses. Conclusion. VitC sufficiency favorably modulates macrophage function. In vivo or in vitro VitC supplementation restores macrophage phenotype and function leading to timely resolution of inflammation.

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“…The work of others supports this hypothesis by demonstrating that gal-1 indeed favors the conversion of peripheral macrophages toward the M2 phenotype and deactivates M1 microglia within the CNS. 30,31 The view of tumor inflammatory status as a principle determinant of immature myeloid cell function helps explain why we and others investigating experimental glioma models with enhanced inflammatory characteristics ascribe antitumor activity to a population of myeloid cells conventionally thought to mediate immune regulatory effects in the context of cancer. 39,51,52 Our experiments with gal-1-deficient glioma reveal the capability of Gr-1 C /CD11b C cells to have immunostimulatory effects.…”

Section: /Cd11bmentioning

confidence: 99%

“…[27][28][29] It has been further proposed that gal-1 dampens inflammatory (M1) monocyte/macrophage activities, in turn favoring those that are anti-inflammatory (M2) and pro-tumor. 30,31 Our own work has shown that mouse GL26 and rat CNS-1 glioma suppress NK-mediated tumor killing by expressing high-levels of this lectin. 32 Tumor-derived lactate dehydrogenase 5 (LDH5) represents an additional mechanism of innate immune suppression in human glioma causing the upregulation of NKG2D ligands on monocytes and leading to NK exhaustion and tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Natural killer cells require monocytic Gr-1⁺/CD11b⁺myeloid cells to eradicate orthotopically engrafted glioma cells

et al. 2016

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Malignant gliomas are resistant to natural killer (NK) cell immune surveillance. However, the mechanisms used by these cancers to suppress antitumor NK cell activity remain poorly understood. We have recently reported on a novel mechanism of innate immune evasion characterized by the overexpression of the carbohydrate-binding protein galectin-1 by both mouse and rat malignant glioma. Here, we investigate the cytokine profile of galectin-1-deficient GL26 cells and describe the process by which these tumors are targeted by the early innate immune system in RAG1¡/¡ and C57BL/6J mice. Our data reveal that galectin-1 knockdown in GL26 cells heightens their inflammatory status leading to the rapid recruitment of Gr-1C myeloid cells and NK1.1 C NK cells into the brain tumor microenvironment, culminating in tumor clearance. We show that immunodepletion of Gr-1 C myeloid cells in RAG1 ¡/¡ mice permits the growth of galectin-1-deficient glioma despite the presence of NK cells, thus demonstrating an essential role for myeloid cells in the clearance of galectin-1-deficient glioma. Further characterization of tumor-infiltrating Gr-1C cells reveals that these cells also express CCR2 and Ly-6C, markers consistent with inflammatory monocytes. Our results demonstrate that Gr-1C myeloid cells, often referred to as myeloid-derived suppressor cells (MDSCs), are required for antitumor NK cell activity against galectin-1-deficient GL26 glioma. We conclude that glioma-derived galectin-1 represents an important factor in dictating the phenotypic behavior of monocytic Gr-1 C

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Galectin-1 induces 12/15-lipoxygenase expression in murine macrophages and favors their conversion toward a pro-resolving phenotype

Cited by 44 publications

References 60 publications

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Resolution of Sterile Inflammation: Role for Vitamin C

Natural killer cells require monocytic Gr-1⁺/CD11b⁺myeloid cells to eradicate orthotopically engrafted glioma cells

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Galectin-1 induces 12/15-lipoxygenase expression in murine macrophages and favors their conversion toward a pro-resolving phenotype

Cited by 44 publications

References 60 publications

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Resolution of Sterile Inflammation: Role for Vitamin C

Natural killer cells require monocytic Gr-1+/CD11b+myeloid cells to eradicate orthotopically engrafted glioma cells

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Natural killer cells require monocytic Gr-1⁺/CD11b⁺myeloid cells to eradicate orthotopically engrafted glioma cells