The acute inflammatory response induced in mice by the venom of the giant ant Dinoponera quadriceps involves macrophage and interleukin-1β. (July 2016)

• Record Type: Journal Article
• Authors: Sousa, Paloma L.; Quinet, Yves P.; Cavalcante Brizeno, Luiz André; Sampaio, Tiago Lima; Torres, Alba Fabíola C.; Martins, Alice Maria C.; Assreuy, Ana Maria S.
• Is Part Of: Toxicon. Volume 117(2016)
• Page Start: 22
• Page End: 29
• Publication Date: 2016-07
• Subjects: Inflammation -- Ant venom -- Ponerinae -- Macrophage -- Interleukin-1 beta; MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- DqV D. Quadriceps venom -- DMSO Dimethylsulfoxide -- ELISA Enzyme Linked Immuno Sorbent Assay -- HE Eosin and hematoxylin -- i.v. Intravenous -- LDH Lactate dehydrogenase -- L-NAME L-NG-Nitroarginine Methyl Ester -- NO nitric oxide -- PBS Phosphate-buffered saline -- PGE1 Prostaglandin E1 -- PGI2 Prostaglandin I2 -- SDS-PAGE Sodium dodecyl sulfate–polyacrylamide gel electrophoresis -- SDS Sodium dodecyl sulphate -- s.c. subcutaneous; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2016.03.009
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: Dinoponera quadriceps (Hymenoptera, Formicidae, Ponerinae) is a primitive and endemic ant of Northeastern Brazil, that uses its sting and associated venom gland to capture preys and for defense. Venom of Dinoponera is of potential clinical importance, since it causes intense local pain, accompanied by erythema and edema, when injected by the sting. With other hymenopteran venoms, inflammatory effects are also reported. The aim of this study was to evaluate the inflammatory activity of D. quadriceps venom (DqV) in mice. Acrylamide electrophoresis of DqV revealed five main protein bands varying between 15 and 100 kDa, confirming the proteinous nature of DqV. DqV subplantar injection elicited edema at 5 μg/kg (3 fold), 50 μg/kg (4 fold) or 500 μg/kg (7 fold) from zero to 360 min compared to saline. DqV (50 μg/kg) increased vascular permeability (4 fold) in the first hour after induction. The paw tissue histology showed moderate inflammatory focus caused by DqV (50 μg/kg) in the first hour of paw edema, but severe tissue changes (edema, inflammatory infiltrate and focal areas of hemorrhage) in the third hour. Intraperitoneal injection of DqV (50 μg/kg) stimulated neutrophil (7 fold) and mononuclear (1.4 fold) migration vs saline. DqV edematogenic effect was inhibited by dexamethasone (92%), thalidomide (82%), cyproheptadine (62%), AA861 (58%), celecoxib (34%) orl -NAME (34%), but the neutrophil migration was only by dexamethasone (57%). DqV-elicited neutrophil migration at 50 μg/kg was potentiated 1.7 fold by the animals pre-treatment with 3% thioglycolate. DqV injection increased the levels of interleukin-1 beta (IL-1β) in peritoneal cavities. DqV (50, 100 and 200 μg/mL) increased phospholipase activity (A425nm ) from 10 min to 40 min. Raw 267 macrophages incubated with DqV (from 3.12 to 50 mg/mL) showed no significant decrease in cell viability or LDH measurements and at 35 μg/mL induced increase in IL-1β (from 3 to 6 h). This study demonstrated, in mice, the inflammatory effect of D. quadriceps venom, characterized by edema, increase in vascular permeability and neutrophil migration, implying the participation of resident macrophages and IL-1β, among other inflammatory mediators. Graphical abstract: Highlights: This is the first demonstration of the inflammatory effect of the venom of the giant ant Dinoponera quadriceps (DqV). The acute inflammatory response induced by DqV is mediated by macrophages and IL-1β. DqV is devoid of toxicity in cultured macrophages. This study brings light for the potential medical interest of ant venoms.