Galectins distinctively regulate central monocyte and macrophage function |
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Authors: | Paclik Daniela Werner Lael Guckelberger Olaf Wiedenmann Bertram Sturm Andreas |
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Institution: | aDepartment of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, Germany;bDepartment of General, Visceral and Transplantation Surgery, Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, Germany |
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Abstract: | Monocytes and macrophages link the innate and adaptive immune systems and protect the host from the outside world. In inflammatory disorders their activation leads to tissue damage. Galectins have emerged as central regulators of the immune system. However, if they regulate monocyte/macrophage physiology is still unknown.Binding of Gal-1, Gal-2, Gal-3 and Gal-4 to monocytes/macrophages, activation, cytokine secretion and apoptosis were determined by FACS, migration by Transwell system and phagocytosis by phagotest. Supernatants from macrophages co-cultured with galectins revealed their influence on T-cell function.In our study Gal-1, Gal-2, Gal-4, and partly Gal-3 bound to monocytes/macrophages. Galectins prevented Salmonella-induced MHCII upregulation. Cytokine release was distinctly induced by different galectins. T-cell activation was significantly restricted by supernatants of macrophages co-cultured in the presence of Gal-2 or Gal-4. Furthermore, all galectins tested significantly inhibited monocyte migration. Finally, we showed for the first time that galectins induce potently monocyte, but not macrophage apoptosis.Our study provides evidence that galectins distinctively modulate central monocyte/macrophage function. By inhibiting T-cell function via macrophage priming, we show that galectins link the innate and adaptive immune systems and provide new insights into the action of sugar-binding proteins. |
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Keywords: | Abbreviations: Gal galectin CRD carbohydrate recognition domain CD Crohn´ s disease UC ulcerative colitis PBMC peripheral blood mononuclear cells MFI mean fluorescence intensity MHCII major histocompatibility complex class II |
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