TCTP from Loxosceles Intermedia (Brown Spider) Venom Contributes to the Allergic and Inflammatory Response of Cutaneous Loxoscelism

Marianna Boia-Ferreira; Kamila G Moreno; Alana B C Basílio; Lucas P da Silva; Larissa Vuitika; Bruna Soley; Ana Carolina M Wille; Lucélia Donatti; Katia C Barbaro; Olga M Chaim; Luiza Helena Gremski; Silvio S Veiga; Andrea Senff-Ribeiro

doi:10.3390/cells8121489

TCTP from Loxosceles Intermedia (Brown Spider) Venom Contributes to the Allergic and Inflammatory Response of Cutaneous Loxoscelism

Cells. 2019 Nov 22;8(12):1489. doi: 10.3390/cells8121489.

Affiliations

¹ Department of Cell Biology, Federal University of Paraná, Curitiba 81531-980, PR, Brazil.
² Department of Pharmacology, Federal University of Paraná, Curitiba 81531-980, PR, Brazil.
³ Department of Structural and Molecular Biology, State University of Ponta Grossa, Ponta Grossa 84030-900, PR, Brazil.
⁴ Laboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, SP, Brazil.
⁵ Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.

Abstract

LiTCTP is a toxin from the Translationally Controlled Tumor Protein (TCTP) family identified in Loxosceles brown spider venoms. These proteins are known as histamine-releasing factors (HRF). TCTPs participate in allergic and anaphylactic reactions, which suggest their potential role as therapeutic targets. The histaminergic effect of TCTP is related to its pro-inflammatory functions. An initial characterization of LiTCTP in animal models showed that this toxin can increase the microvascular permeability of skin vessels and induce paw edema in a dose-dependent manner. We evaluated the role of LiTCTP in vitro and in vivo in the inflammatory and allergic aspects that undergo the biological responses observed in Loxoscelism, the clinical condition after an accident with Loxosceles spiders. Our results showed LiTCTP recombinant toxin (LiRecTCTP) as an essential synergistic factor for the dermonecrotic toxin actions (LiRecDT1, known as the main toxin in the pathophysiology of Loxoscelism), revealing its contribution to the exacerbated inflammatory response clinically observed in envenomated patients.

Keywords: HRF; Loxosceles; TCTP; brown spider; toxin; venom.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers, Tumor / antagonists & inhibitors
Biomarkers, Tumor / genetics
Biomarkers, Tumor / immunology*
Cimetidine / administration & dosage
Cimetidine / pharmacology
Cromolyn Sodium / administration & dosage
Cromolyn Sodium / pharmacology
Dose-Response Relationship, Drug
Hypersensitivity / drug therapy
Hypersensitivity / immunology*
Inflammation / drug therapy
Inflammation / immunology*
Injections, Intraperitoneal
Injections, Intravenous
Mast Cells / drug effects
Mast Cells / immunology
Mice
Phosphoric Diester Hydrolases / chemistry*
Phosphoric Diester Hydrolases / immunology*
Piperidines / administration & dosage
Piperidines / pharmacology
Promethazine / administration & dosage
Promethazine / pharmacology
Rabbits
Rats
Skin Diseases / drug therapy
Skin Diseases / immunology*
Spider Venoms / chemistry*
Spider Venoms / immunology*
Tumor Cells, Cultured
Tumor Protein, Translationally-Controlled 1

Substances

Biomarkers, Tumor
Piperidines
Spider Venoms
Tpt1 protein, mouse
Tpt1 protein, rat
Tumor Protein, Translationally-Controlled 1
loxosceles venom
Cimetidine
Phosphoric Diester Hydrolases
Promethazine
thioperamide
Cromolyn Sodium