A GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus modulates immune response in macrophages and in mice

Abstract

A GalNAc/Gal-specific lectin (CGL) from the edible mussel Crenomytilus grayanus has been demonstrated to exhibit antibacterial properties. However, the mechanism of immune modulation by CGL in mammalian cells remains unclear. Here, we demonstrated that CGL can activate immune responses in macrophages and in mice. In the in vitro cell models, CGL induced tumour necrosis factor-α and interleukin-6 secretion in mouse RAW264.7 macrophages, mouse bone marrow-derived macrophages, human THP-1 macrophages, human peripheral blood mononuclear cells and human blood monocyte-derived macrophages. The CGL-mediated cytokine production was regulated by reactive oxygen species, mitogen-activated protein kinases, protein kinase C-α/δ and NF-κB. Interestingly, in lipopolysaccharide-activated macrophages, CGL induced endotoxin tolerance (characterized by the downregulation of nitric oxide, inducible nitric oxide synthase, interleukin-6 and cyclooxygenase II) via the downregulation of IRAK2 expression, JNK1/2 phosphorylation and NF-κB activation. CGL also slightly increased the bactericidal activity of macrophages and induced cytokine production in mouse models. Overall, our data indicate that CGL has the potential to be used as an immune modulator in mammals.

Activity Dependence of a Novel Lectin Family on Structure and Carbohydrate-Binding Properties

“…In addition, it also obviously decreased the response to LPS stimulus by reducing secretion of IL-6, generation of NO, expression of iNOS and COX-2. However, this did not affect the secretion of TNF-α [49]. CGL-induced endotoxin tolerance might be due to decreased expression of IRAK2, an important signaling molecule that is important in pathway of NF-κB activation mediated by TLR [53].…”

“…To understand whether TNF-α production mediated by CGL was due to protein-carbohydrate interaction, lectin was incubated with sugars before adding to macrophages. No effect was observed on TNF-α production, suggesting that cytokine production induced by CGL was independent of its carbohydrate binding properties [49].…”

“…CGL also induced the production of TNF-α and IL-6 in the RAW264.7 mouse macrophage cell line (Figure 4a) and in the human macrophage cell line THP-1 (Figure 4b). CGL also induced cytokine production in primary cells: macrophages derived from mouse bone marrow, mononuclear cells in human peripheral blood, and macrophages derived from human blood monocytes [49].…”

“…Further it was shown that CGL not only induces cytokine expression, but improves the bactericidal activity of macrophages [49]. The bactericidal activity of macrophages is characterized by increased phagocytosis and bacterial death.…”

A GM1b/asialo‐GM1 oligosaccharide‐binding R‐type lectin from purplish bifurcate mussels Mytilisepta virgata and its effect on MAP kinases

“…Both MytiLec‐1 and SeviL therefore can potentially regulate the growth of human cancer cells by binding their respective ligands and activating similar metabolic pathways (Figs and ). The mytilectin family is known to play roles not only in the regulation of cell death and also cell proliferation , through the activation of kinases. SeviL and the other R‐type lectins isolated from Mytilidae may similarly have multiple activities, and it is possible that their expression may be regulated by signals external to the organism.…”