Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils

Karlsson, Anna; Christenson, Karin; Matlak, Mustafa; Björstad, Åse; Brown, Kelly L.; Telemo, Esbjörn; Salomonsson, Emma; Leffler, Hakon; Bylund, Johan

doi:10.1093/glycob/cwn104

Cited by 137 publications

(120 citation statements)

References 18 publications

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“…Moreover, MacKinnon et al have shown that up-regulation of galectin-3 expression is a feature of the alternative macrophage (M2) phenotype and that release of galectin-3 by alternatively activated macrophages sustains the M2 phenotype contributing to some of its functions in vivo [68]. For instance, Karlsson et al showed that galectin-3, by functioning as an opsonin, favors the phagocytic clearance of apoptotic neutrophils by macrophages, a process of crucial importance for termination of acute inflammation [69]. Accordingly, Caberoy et al have recently demonstrated that galectin-3 is a legitimate MerTK-specific "eat-me" signal which stimulates phagocytosis of apoptotic cells and cellular debris [70].…”

Section: Galectin-3 As a Disease Mediator: Animal Studiesmentioning

confidence: 99%

Galectin-3 in diabetic patients

Pugliese

Iacobini

Ricci

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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Galectin-3 is a versatile molecule which exerts several and sometimes opposite functions in various pathophysiological processes. Recently, galectin-3 has gained attention as a powerful predictor of heart failure and mortality, thus becoming a useful prognostic marker in clinical practice. Moreover, though not specifically investigated in diabetic cohorts, plasma levels of galectin-3 correlated with the prevalence of diabetes and related metabolic conditions, thus suggesting that pharmacological blockade of this lectin might be successful for treating heart failure especially in subjects suffering from these disorders. Indeed, galectin-3 is considered not only as a marker of heart failure, but also as a mediator of the disease, due to its pro-fibrotic action, though evidence comes mainly from studies in galectin-3 deficient mice. However, these studies have provided contrasting results, with either attenuation or acceleration of organ fibrosis and inflammation, depending on the experimental setting and particularly on the levels of advanced glycation endproducts (AGEs)/advanced lipoxidation endproducts (ALEs), of which galectin-3 is a scavenging receptor. In fact, under conditions of increased AGE/ALE levels, galectin-3 ablation was associated with tissue-specific outcomes, reflecting the AGE/ALE-receptor function of this lectin. Conversely, in experimental models of acute inflammation and fibrosis, galectin-3 deficiency resulted in attenuation of tissue injury. There is a need for prospective studies in diabetic patients specifically investigating the relation of galectin-3 levels with complications and for further animal studies in order to establish the effective role of this lectin in organ damage before considering its pharmacological blockade in the clinical setting.

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Section: Galectin-3 As a Disease Mediator: Animal Studiesmentioning

confidence: 99%

Galectin-3 in diabetic patients

Pugliese

Iacobini

Ricci

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Gal-3 has been found to play a critical role in macrophage phagocytosis with Gal-3 null macrophages demonstrating decreased phagocytosis of IgG-opsonised erythrocytes and thymocytes in vitro; moreover, Gal-3 null mice display reduced phagocytosis of red blood cells by kupffer cells in a model of haemolytic anaemia (Sano et al 2003). Treatment with hr-Gal-3 increases phagocytosis of apoptotic neutrophils by monocyte-derived macrophages (Karlsson et al 2008), and this is in agreement with the fact that Gal-3 null macrophages demonstrate reduced phagocytosis of apoptotic neutrophils . As well as increasing macrophage phagocytosis, Gal-3 also enhances the phagocytic capabilities of neutrophils, a fact that may in part account for the protective role of Gal-3 in infections such as S. pneumoniae .…”

Section: Actions Of Exogenous Galectin-3mentioning

confidence: 99%

Endogenous galectins and the control of the host inflammatory response

Norling¹,

Perretti²,

Cooper³

2009

Journal of Endocrinology

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A new era of research is being devoted to deciphering endogenous mediators and mechanisms that are in place to resolve the inflammatory response. Accruing evidence indicates that galectins fall into this category of immunoregulatory mediators signifying their use as prospective novel anti-inflammatory agents. The focus of this review is to depict the immunoregulatory bioactivities of three members of the galectin superfamily, Galectin (Gal)-1, Gal-3 and Gal-9.Emphasis is given to the studies investigating the properties of these endogenous lectins. Gal-1, Gal-3 and Gal-9 are emerging as pertinent players in the modulation of acute and chronic inflammatory diseases, autoimmunity and cancer, and thus being increasingly recognised as molecular targets for innovative drug discovery.

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“…Apoptotic neutrophils display a distinct surface molecular phenotype important for attenuation of functional responses (9) with additional surface changes that target dying cells for removal by phagocytes (10). A number of soluble factors present in serum, including complement C1q and C3b, properdin, collectins, long pentraxin-3, MFG-E8, galectin-3, and ␣ 2 -macroglobulin, have been reported to bind to apoptotic human cells (11)(12)(13)(14)(15)(16)(17)(18) and consequently modulate their recognition and uptake by macrophages via a number of different surface receptors, including scavenger receptors, complement receptors, receptors for phosphatidylserine, and Mertk (19 -22). However, it is important to note that some of these opsonization events occur relatively late during the apoptotic process and accompany loss of membrane integrity (23).…”

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confidence: 99%

Glucocorticoids Induce Protein S-Dependent Phagocytosis of Apoptotic Neutrophils by Human Macrophages

McColl

Bournazos

Franz

et al. 2009

The Journal of Immunology

115

119

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During resolution of an inflammatory response, recruited neutrophil granulocytes undergo apoptosis and are removed by tissue phagocytes before induction of secondary necrosis without provoking proinflammatory cytokine production and release. Promotion of physiological neutrophil clearance mechanisms may represent a viable therapeutic strategy for the treatment of inflammatory or autoimmune diseases in which removal of apoptotic cells is impaired. The mechanism underlying enhancement of macrophage capacity for phagocytosis of apoptotic cells by the powerful anti-inflammatory drugs of the glucocorticoid family has remained elusive. In this study, we report that human monocyte-derived macrophages cultured in the presence of dexamethasone exhibit augmented capacity for phagocytosis of membrane-intact, early apoptotic cells only in the presence of a serum factor. Our results eliminate a role for a number of potential opsonins, including complement, pentraxin-3, and fibronectin. Using ion-exchange and gel filtration chromatography, we identified a high molecular mass serum fraction containing C4-binding protein and protein S responsible for the augmentation of phagocytosis of apoptotic neutrophils. Because the apoptotic neutrophils used in this study specifically bind protein S, we suggest that glucocorticoid treatment of macrophages induces a switch to a protein S-dependent apoptotic cell recognition mechanism. Consistent with this suggestion, pretreatment of macrophages with Abs to Mer tyrosine kinase, a member of the Tyro3/Axl/Mer family of receptor tyrosine kinases, prevented glucocorticoid augmentation of phagocytosis. Induction of a protein S/Mer tyrosine kinase-dependent apoptotic cell clearance pathway may contribute to the potent anti-inflammatory effects of glucocorticoids, representing a potential target for promoting resolution of inflammatory responses.

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Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils

Cited by 137 publications

References 18 publications

Galectin-3 in diabetic patients

Galectin-3 in diabetic patients

Endogenous galectins and the control of the host inflammatory response

Glucocorticoids Induce Protein S-Dependent Phagocytosis of Apoptotic Neutrophils by Human Macrophages

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