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Loxosceles venom Sphingomyelinase D activates human blood leukocytes: Role of the complement system

Manzoni-de-Almeida, Daniel, Squaiella-Baptistao, Carla Cristina, Lopes, Priscila Hess, van den Berg, Carmen W. and Tambourgi, Denise V. 2018. Loxosceles venom Sphingomyelinase D activates human blood leukocytes: Role of the complement system. Molecular Immunology 94 , pp. 45-53. 10.1016/j.molimm.2017.12.009

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Abstract

Envenomation by Loxosceles spiders can result in severe systemic and local reactions, which are mainly triggered by Sphingomyelinase D (SMase D), a toxic component of Loxosceles venom. SMase D induces a systemic inflammatory condition similar to the reaction observed during an endotoxic shock. Considering the potent pro-inflammatory potential of Loxosceles venom and the SMase D, in this study we have used the whole human blood model to study the endotoxic-like shock triggered by SMase D. Recombinant purified SMase D from L. intermedia venom, similarly to LPS, induced activation of blood leukocytes, as observed by the increase in the expression of CD11b and TLR4, production of reactive oxygen and nitrogen species (superoxide anion and peroxynitrite) and release of TNF-α. Complement consumption in the plasma was also detected, and complement inhibition by compstatin decreased the SMase D and LPS-induced leukocyte activation, as demonstrated by a reduction in the expression of CD11b and TLR4 and superoxide anion production. Similar results were found for the L. intermedia venom, except for the production of TNF-α. These findings indicate that SMase D present in Loxosceles venom is able to activate leukocytes in a partially complement-dependent manner, which can contribute to the systemic inflammation that follows envenomation by this spider. Thus, future therapeutic management of systemic Loxosceles envenomation could include the use of complement inhibitors as adjunct therapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0161-5890
Date of Acceptance: 8 December 2017
Last Modified: 07 Aug 2018 10:15
URI: http://orca.cf.ac.uk/id/eprint/113922

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