Extracellular matrix molecules as targets for brown spider venom toxins

Abstract

Loxoscelism, the term used to describe lesions and clinical manifestations induced by brown spiders 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. Correspondence

‘Partitagin’ a hemorrhagic metalloprotease from Hippasa partita spider venom: Role in tissue necrosis

“…Selected and/or limited cleavages of key peptide bonds of basement membrane proteins of blood vessel endothelium appear to weaken the capillary wall leading to extravasation. Similar observations were made with the studies using L. intermedia venom [13]. Infiltration and confluence of PMNLs are a natural response for tissue destruction, and this could be due to the action of Partitagin resulting in generation of PMNLs recruiting proteolytic peptide fragments either from collagen type IV or fibronectin or from both.…”

“…Immunofluorescence staining studies indicated the association of fibronectin with the subendothelial extracellular matrix. Degradation of fibronectin will render the structure of the endothelium more susceptible for damage [12,13,16]. Thus, degradation of basement membrane collagen type-IV and fibronectin molecules in the blood vessels appears to be the key process for the hemorrhage caused by Partitagin and probably whole venom as well.…”

Venomous protease of aphid soldier for colony defense

“…However, it is not a digestive enzyme but is used as a venomous molecule for attacking enemies. Venom proteases are found in snakes, spiders, and other venomous animals (39,40). In these predatory animals, it is plausible that the proteases were derived from salivary or intestinal proteases for digestion.…”

Desenlace fatal por loxoscelismo cutáneo visceral: Report of one case

“…Se ha reportado el depósito de componentes del veneno en glomérulos, células del epitelio tubular y membranas basales renales 13 . Se ha demostrado que una metaloproteasa actúa sobre estructuras de la membrana basal como la entactina, proteoglicanos y componentes de la matriz celular 14,15 . Esto ha sugerido que la acción directa del veneno podría llevar a la pérdida de la integridad de vasos y glomérulos, resultando en hemorragia y alteraciones renales 14 .…”

“…Lo anterior puede explicarse por la acción de componentes del veneno, que producen daño al asociarse directamente a estructuras del riñón [13][14][15] , dificultando la resolución de la IRA. Además, otros insultos pudieron haber contribuido a aumentar el daño renal, así como a la perpetuación de la NTA: la inestabilidad hemodinámica observada durante las diálisis y episodios de taquiarritmias, sepsis (por la neumonía aspirativa, que si bien fue tratada oportunamente, pudo haber favorecido en algún grado el daño renal).…”