Extracellular matrix molecules as targets for brown spider venom toxins.

S.S Veiga,O.C Mangili,V.C Zanetti,A Braz,W Gremski

doi:10.1590/s0100-879x2001000700002

S.S Veiga, O.C Mangili + Show 3 more

Open Access

https://doi.org/10.1590/s0100-879x2001000700002

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Abstract

Loxoscelism, the term used to describe lesions and clinical manifestations induced by brown spider's venom (Loxosceles genus), has attracted much attention over the last years. Brown spider bites have been reported to cause a local and acute inflammatory reaction that may evolve to dermonecrosis (a hallmark of envenomation) and hemorrhage at the bite site, besides systemic manifestations such as thrombocytopenia, disseminated intravascular coagulation, hemolysis, and renal failure. The molecular mechanisms by which Loxosceles venoms induce injury are currently under investigation. In this review, we focused on the latest reports describing the biological and physiopathological aspects of loxoscelism, with reference mainly to the proteases recently described as metalloproteases and serine proteases, as well as on the proteolytic effects triggered by L. intermedia venom upon extracellular matrix constituents such as fibronectin, fibrinogen, entactin and heparan sulfate proteoglycan, besides the disruptive activity of the venom on Engelbreth-Holm-Swarm basement membranes. Degradation of these extracellular matrix molecules and the observed disruption of basement membranes could be related to deleterious activities of the venom such as loss of vessel and glomerular integrity and spreading of the venom toxins to underlying tissues.

Highlights

Brown spiders (Loxosceles genus) have been reported to cause several clinical manifestations
We focused on the latest reports describing the biological and physiopathological aspects of loxoscelism, with reference mainly to the proteases recently described as metalloproteases and serine proteases, as well as on the proteolytic effects triggered by L. intermedia venom upon extracellular matrix constituents such as fibronectin, fibrinogen, entactin and heparan sulfate proteoglycan, besides the disruptive activity of the venom on Engelbreth-Holm-Swarm basement membranes
The molecular mechanisms by which the brown spider venoms cause dermonecrotic injury, local and systemic hemorrhage, thrombocytopenia, hemolysis, disseminated intravascular coagulation and renal failure are currently under investigation, but since the venom is composed of a mixture of several proteins, these mechanisms seem to be molecularly complex and may be dependent on many different toxins

Summary

Introduction

Brown spiders (Loxosceles genus) have been reported to cause several clinical manifestations. Envenomation provokes two major kinds of signals, i.e., local lesions at the bite site characterized by edema followed by vasodilatation, blood vessel degeneration, local hemorrhage and a significant cutaneous tissue injury with gravitational spreading, that can exacerbate to necrotic skin ulcers and degeneration [1,2,3,4], and systemic effects that begin as a malaise and can become generalized, with hemolysis, thrombocytopenia, disseminated intravascular coagulation and renal failure These clinical signs and toxicological effects appear to be phenomena similar for several Loxosceles species including the more studied L. reclusa, L. laeta, L. intermedia and L. gaucho species [4,5,6,7,8]. Soluble plasma fibrinogen is the major substrate in this family, but it is not the only one since snake venom actions on laminin, entactin, fibronectin and

Action of brown spider venom on basement membrane constituents

Concluding remarks and future expectations