Galectin-3: A Positive Regulator of Leukocyte Recruitment in the Inflamed Microcirculation

Abstract

In vivo and ex vivo imaging was used to investigate the function of galectin-3 (Gal-3) during the process of leukocyte recruitment to the inflamed microcirculation. The cremasteric microcirculation of wild-type (C57BL/6), Gal-3 -/-and CX 3 CR1 gfp/+ mice was assessed by intravital microscopy following PBS, IL-1β, TNF-α or recombinant Gal-3 treatment. These cellular responses were investigated further using flow-chamber assays, confocal microscopy, flow cytometry, PCR analysis and proteome array. We show that mechanisms mediating leukocyte slow rolling and emigration are impaired in Gal-3 -/-mice, which could be due to impaired expression of cell adhesion molecules and an altered cell surface glycoproteome. Local (intrascrotal) administration of recombinant Gal-3 to wild-type mice resulted in a dose-dependent reduction in rolling velocity associated with increased numbers of adherent and emigrated leukocytes, approximately 50% of which were Ly6G-positive neutrophils. Intrascrotal administration of Gal-3 to CX 3 CR1 gfp/+ mice confirmed that approximately equal numbers of monocytes are also recruited in response to this lectin. Exogenous Gal-3 treatment was accompanied by increased proinflammatory cytokines and chemokines within the local tissue. In conclusion, this study unveils novel biology for both exogenous and endogenous Gal-3 in promoting leukocyte recruitment during acute inflammation.

Galectin‐3 and risk of atrial fibrillation: A systematic review and meta‐analysis

“…Galectin‐3 was originally discovered in 1982 as Mac‐2, cloned in 1991, and subsequently recognized as a β‐galactoside‐binding lectin . It has diverse biological functions such as regulation of cell adhesion, immunity, inflammation, and fibrosis . Its pathological role in the heart, specifically heart failure, has been discussed in detail by the excellent review here .…”

Histochemical characteristics of regressing vessels in the hyaloid vascular system of neonatal mice: Novel implication for vascular atrophy

“…Galectin-3 functions as a chemoattractant molecule for macrophages (Sano et al, 2000;Gittens et al, 2017) and plays a role of opsonins in enhancing the phagocytic clearance of apoptotic cells but not viable cells by macrophages (Karlsson et al, 2009). In final stages of regression, released galectin-3 may be involved in drawing of macrophages and subsequent engulfment of apoptotic cells.…”

Utilization of Galectins by Pathogens for Infection

“…In addition, because Gal-3 primarily interacts with internal LacNAc motifs, α-2,6 sialylation of terminal glycans does not abolish binding by Gal-3 (22,155). Gal-3 is associated with a high proinflammatory cytokine production (156)(157)(158) and leukocyte recruitment (159) and thus is believed to have a predominant proinflammatory function. Additionally, Gal-3 suppresses Th17 response (e.g., H. capsulatum), NO production (e.g., C. albicans), and autophagy (e.g., Group A Streptococcus).…”