Galectin-3–null mice display defective neutrophil clearance during acute inflammation

Wright, Rachael D.; Souza, Patricia R.; Flak, Magdalena B.; Thedchanamoorthy, Prasheetha; Norling, Lucy V.; Cooper, Dianne

doi:10.1189/jlb.3a0116-026rr

Cited by 24 publications

(23 citation statements)

References 29 publications

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“…There were, however, elevated chemerin levels in the blood of the Ccrl2 − / − mice compared with WT controls (Figure 4 I). As we did not observe any differences in neutrophil numbers in the blood of these animals, it seems unlikely there would be changes in the bone marrow at this early time point but this was not assessed ( 53 ). Collectively, these observations demonstrate that mice lacking Ccrl2 display exaggerated neutrophil recruitment to local sites of inflammation as well as elevated chemerin and CXCL1 levels irrespective of the stimulus used to elicit the response.…”

Section: Resultsmentioning

confidence: 78%

Absence of the Non-Signalling Chemerin Receptor CCRL2 Exacerbates Acute Inflammatory Responses In Vivo

et al. 2017

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Chemerin is a chemotactic protein that induces migration of several immune cells including macrophages, immature dendritic cells, and NK cells. Chemerin binds to three G protein-coupled receptors (GPCRs), including CCRL2. The exact function of CCRL2 remains unclear. CCRL2 expression is rapidly upregulated during inflammation, but it lacks the intracellular DRYLAIV motif required for classical GPCR downstream signalling pathways, and it has not been reported to internalise chemerin upon binding. The aim of this study was to investigate what role if any CCRL2 plays during acute inflammation. Using the zymosan- and thioglycollate-induced murine models of acute inflammation, we report that mice deficient in the Ccrl2 gene display exaggerated local and systemic inflammatory responses, characterised by increased myeloid cell recruitment. This amplified myeloid cell recruitment was associated with increased chemerin and CXCL1 levels. Furthermore, we report that the inflammatory phenotype observed in these mice is dependent upon elevated levels of endogenous chemerin. Antibody neutralisation of chemerin activity in Ccrl2−/− mice abrogated the amplified inflammatory responses. Importantly, chemerin did not directly recruit myeloid cells but rather increased the production of other chemotactic proteins such as CXCL1. Administration of recombinant chemerin to wild-type mice before inflammatory challenge recapitulated the increased myeloid cell recruitment and inflammatory mediator production observed in Ccrl2−/− mice. We have demonstrated that the absence of CCRL2 results in increased levels of local and systemic chemerin levels and exacerbated inflammatory responses during acute inflammatory challenge. These results further highlight the importance of chemerin as a therapeutic target in inflammatory diseases.

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Section: Resultsmentioning

confidence: 78%

Absence of the Non-Signalling Chemerin Receptor CCRL2 Exacerbates Acute Inflammatory Responses In Vivo

et al. 2017

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“…Gal-3 is a central regulator of critical processes under the setting of acute and chronic inflammation. Gal-3 is involved in the process of acute inflammatory response including chemoattraction of monocytes/macrophages [19], neutrophil clearance [20], opsonization of apoptotic neutrophils [21], and mast cell degranulation [22]. Through interacting with nucleotide oligomerization domain-like receptor protein 3 (NLRP3), intracellular Gal-3 enhanced the effects of H5N1 infection by promoting host inflammatory responses and regulating interleukin-1 beta (IL-1β) production by macrophages.…”

Section: Gal-3 and Inflammationmentioning

confidence: 99%

Galectin-3 Is a Potential Mediator for Atherosclerosis

Gao

Liu

Wang

et al. 2020

Journal of Immunology Research

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Atherosclerosis is a multifactorial chronic inflammatory arterial disease forming the pathological basis of many cardiovascular diseases such as coronary heart disease, heart failure, and stroke. Numerous studies have implicated inflammation as a key player in the initiation and progression of atherosclerosis. Galectin-3 (Gal-3) is a 30 kDa β-galactose, highly conserved and widely distributed intracellularly and extracellularly. Gal-3 has been demonstrated in recent years to be a novel inflammatory factor participating in the process of intravascular inflammation, lipid endocytosis, macrophage activation, cellular proliferation, monocyte chemotaxis, and cell adhesion. This review focuses on the role of Gal-3 in atherosclerosis and the mechanism involved and several classical Gal-3 agonists and antagonists in the current studies.

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“…However, this conclusion is in contrast with previous data suggesting a critical role for this lectin in osteoclast differentiation and function [ 40 , 47 ]. Moreover, from these data, it cannot be ruled-out a protective role mediated by the anti-inflammatory, pro-resolution effect of galectin-3 [ 20 , 27 , 28 , 29 , 30 , 95 ]. Likewise, it cannot be excluded the possibility that the pro-osteogenic properties of galectin-3 may have contributed to protection from net bone loss.…”

Section: Galectin-3 In Inflammatory Bone and Joint Disordersmentioning

confidence: 99%

Role of Galectin-3 in Bone Cell Differentiation, Bone Pathophysiology and Vascular Osteogenesis

Iacobini¹,

Fantauzzi²,

Pugliese³

et al. 2017

IJMS

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Galectin-3 is expressed in various tissues, including the bone, where it is considered a marker of chondrogenic and osteogenic cell lineages. Galectin-3 protein was found to be increased in the differentiated chondrocytes of the metaphyseal plate cartilage, where it favors chondrocyte survival and cartilage matrix mineralization. It was also shown to be highly expressed in differentiating osteoblasts and osteoclasts, in concomitance with expression of osteogenic markers and Runt-related transcription factor 2 and with the appearance of a mature phenotype. Galectin-3 is expressed also by osteocytes, though its function in these cells has not been fully elucidated. The effects of galectin-3 on bone cells were also investigated in galectin-3 null mice, further supporting its role in all stages of bone biology, from development to remodeling. Galectin-3 was also shown to act as a receptor for advanced glycation endproducts, which have been implicated in age-dependent and diabetes-associated bone fragility. Moreover, its regulatory role in inflammatory bone and joint disorders entitles galectin-3 as a possible therapeutic target. Finally, galectin-3 capacity to commit mesenchymal stem cells to the osteoblastic lineage and to favor transdifferentiation of vascular smooth muscle cells into an osteoblast-like phenotype open a new area of interest in bone and vascular pathologies.

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Galectin-3–null mice display defective neutrophil clearance during acute inflammation

Abstract: Expression of galectin-3 by exudated neutrophils drives neutrophil apoptosis and clearance in a model of self-resolving peritonitis.

Cited by 24 publications

References 29 publications

Absence of the Non-Signalling Chemerin Receptor CCRL2 Exacerbates Acute Inflammatory Responses In Vivo

Absence of the Non-Signalling Chemerin Receptor CCRL2 Exacerbates Acute Inflammatory Responses In Vivo

Galectin-3 Is a Potential Mediator for Atherosclerosis

Role of Galectin-3 in Bone Cell Differentiation, Bone Pathophysiology and Vascular Osteogenesis

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