title: The acute inflammatory response induced in mice by the venom of the giant ant Dinoponera quadriceps involves macrophage and interleukin-1β.
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%) or l-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.
authors.affiliation: Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará (UECE), Av. Paranjana 1700, Itaperi 60 740-000, Fortaleza-CE, Brazil.
authors.forename: Paloma L
authors.initials: PL
authors.lastname: Sousa
authors.affiliation: Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará (UECE), Av. Paranjana 1700, Itaperi 60 740-000, Fortaleza-CE, Brazil.
authors.forename: Yves P
authors.initials: YP
authors.lastname: Quinet
authors.affiliation: Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará (UECE), Av. Paranjana 1700, Itaperi 60 740-000, Fortaleza-CE, Brazil.
authors.forename: Luiz André
authors.initials: LA
authors.lastname: Cavalcante Brizeno
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará (UFC), Rua Capitão Francisco Pedro 1210, 60430-370, Fortaleza-CE, Brazil.
authors.forename: Tiago Lima
authors.initials: TL
authors.lastname: Sampaio
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará (UFC), Rua Capitão Francisco Pedro 1210, 60430-370, Fortaleza-CE, Brazil.
authors.forename: Alba Fabíola C
authors.initials: AF
authors.lastname: Torres
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará (UFC), Rua Capitão Francisco Pedro 1210, 60430-370, Fortaleza-CE, Brazil.
authors.forename: Alice Maria C
authors.initials: AM
authors.lastname: Martins
authors.affiliation: Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará (UECE), Av. Paranjana 1700, Itaperi 60 740-000, Fortaleza-CE, Brazil. Electronic address: anassreuy@gmail.com.
authors.forename: Ana Maria S
authors.initials: AM
authors.lastname: Assreuy
mesh_terms: D000818:Animals; D000862:Ant Venoms / Q000633:toxicity*; D001000:Ants; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D007249:Inflammation / Q000139:chemically induced; D053583:Interleukin-1beta / Q000378:metabolism / Q000502:physiology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051379:Mice; D010538:Peritonitis / Q000139:chemically induced / Q000473:pathology; D018675:Toxicity Tests
chemical_list: D000862:Ant Venoms; D053583:Interleukin-1beta
keywords: Ant venom; Inflammation; Interleukin-1 beta; Macrophage; Ponerinae