title: Galatrox is a C-type lectin in Bothrops atrox snake venom that selectively binds LacNAc-terminated glycans and can induce acute inflammation.
abstract: Previous studies indicate that snake venom contains glycan-binding proteins (GBPs), although the binding specificity and biological activities of many of these GBPs is unclear. Here we report our studies on the glycan binding specificity and activities of galatrox, a Bothrops atrox snake venom-derived GBP. Glycan microarray analysis indicates that galatrox binds most strongly to glycans expressing N-acetyllactosamine (LacNAc), with a significant preference for Galβ1-4GlcNAcβ over Galβ1-3GlcNAcβ compounds. Galatrox also bound immobilized laminin, a LacNAc-dense extracellular matrix component, suggesting that this GBP can bind LacNAc-bearing glycoproteins. As several endogenous mammalian GBPs utilize a similar binding LacNAc binding preference to regulate neutrophil and monocyte activity, we hypothesized that galatrox may mediate B. atrox toxicity through regulation of leukocyte activity. Indeed, galatrox bound neutrophils and promoted leukocyte chemotaxis in a carbohydrate-dependent manner. Similarly, galatrox administration into the mouse peritoneal cavity induced significant neutrophil migration and the release of pro-inflammatory cytokines IL-1α and IL-6. Exposure of bone marrow-derived macrophages to galatrox induced generation of pro-inflammatory mediators IL-6, TNF-α, and keratinocyte-derived chemokine. This signaling by galatrox was mediated via its carbohydrate recognition domain by activation of the TLR4-mediated MyD88-dependent signaling pathway. These results indicate that galatrox has pro-inflammatory activity through its interaction with LacNAc-bearing glycans on neutrophils, macrophages and extracellular matrix proteins and induce the release of pro-inflammatory mediators.
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040903 São Paulo, Brazil.
authors: Marco A
authors: MA
authors: Sartim
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040903 São Paulo, Brazil.
authors: Thalita B
authors: TB
authors: Riul
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040903 São Paulo, Brazil.
authors: Camillo
authors: C
authors: Del Cistia-Andrade
authors: Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Atlanta 30322, GA, USA.
authors: Sean R
authors: SR
authors: Stowell
authors: Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Atlanta 30322, GA, USA.
authors: Connie M
authors: CM
authors: Arthur
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040903 São Paulo, Brazil.
authors: Carlos A
authors: CA
authors: Sorgi
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040903 São Paulo, Brazil.
authors: Lucia H
authors: LH
authors: Faccioli
authors: Department of Biochemistry and The Glycomics Center, Emory University School of Medicine, Atlanta 30322, GA, USA.
authors: Richard D
authors: RD
authors: Cummings
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040903 São Paulo, Brazil suvilela@usp.br mdbaruff@fcfrp.usp.br.
authors: Marcelo
authors: M
authors: Dias-Baruffi
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040903 São Paulo, Brazil suvilela@usp.br mdbaruff@fcfrp.usp.br.
authors: Suely V
authors: SV
authors: Sampaio
mesh_terms: D000818:Animals; D017837:Bothrops; D002240:Carbohydrate Sequence; D003435:Crotalid Venoms / Q000737:chemistry*; D007249:Inflammation / Q000139:chemically induced*; D037102:Lectins / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000378:metabolism*; D014757:Viper Venoms / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003435:Crotalid Venoms; D037102:Lectins; D011134:Polysaccharides; D014757:Viper Venoms; C557501:galatrox protein, Bothrops atrox
keywords: Bothrops atrox; C-type lectin; Inflammatory response; Neutrophil migration; Snake venom