title: Bothrops jararacussu snake venom-induces a local inflammatory response in a prostanoid- and neutrophil-dependent manner.
abstract: Local tissue reactions provoked by Bothrops venoms are characterized by edema, hemorrhage, pain, and inflammation; however, the mechanisms of tissue damage vary depending upon the species of snake. Here, we investigated the mechanisms involved in the local inflammatory response induced by the Bothrops jararacussu venom (BjcuV). Female Swiss mice were injected with either saline, BjcuV (0.125-8 μg/paw) or loratadine (an H1 receptor antagonist), compound 48/80 (for mast cell depletion), capsaicin (for C-fiber desensitization), infliximab (an anti-TNF-α antibody), indomethacin (a non-specific COX inhibitor), celecoxib (a selective COX-2 inhibitor) or fucoidan (a P- and L-selectins modulator) given before BjcuV injection. Paw edema was measured by plethysmography. In addition, paw tissues were collected for the measurement of myeloperoxidase activity, TNF-α and IL-1 levels, and COX-2 immunoexpression. The direct chemotactic effect of BjcuV and the in vitro calcium dynamic in neutrophils were also investigated. BjcuV caused an edematogenic response with increased local production of TNF-α and IL-1β as well as COX-2 expression. Both edema and neutrophil migration were prevented by pretreatment with indomethacin, celecoxib or fucoidan. Furthermore, BjcuV induced a direct in vitro neutrophil chemotaxis by increasing intracellular calcium. Therefore, BjcuV induces an early onset edema dependent upon prostanoid production and neutrophil migration.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: C W S
authors.initials: CW
authors.lastname: Wanderley
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: C M S
authors.initials: CM
authors.lastname: Silva
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: D V T
authors.initials: DV
authors.lastname: Wong
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: R M
authors.initials: RM
authors.lastname: Ximenes
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: D F C
authors.initials: DF
authors.lastname: Morelo
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Cosker
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: K S
authors.initials: KS
authors.lastname: Aragão
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: College of Veterinary Medicine, Federal University of Vale do São Francisco, Brazil.
authors.forename: R C
authors.initials: RC
authors.lastname: Palheta-Júnior
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Havt
authors.affiliation: Department of Morphology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: G A C
authors.initials: GA
authors.lastname: Brito
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: F Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
authors.forename: R A
authors.initials: RA
authors.lastname: Ribeiro
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil. Electronic address: robertocesarpljr@gmail.com.
authors.forename: R C P
authors.initials: RC
authors.lastname: Lima-Júnior
mesh_terms: D000818:Animals; D017837:Bothrops; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003435:Crotalid Venoms / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D011453:Prostaglandins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D003435:Crotalid Venoms; D053583:Interleukin-1beta; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2
keywords: Bothrops jararacussu venom; Edema; Inflammation; Neutrophil; Prostanoids; Selectins