Loxosceles spider venom induces the release of thrombomodulin and endothelial protein C receptor: implications for the pathogenesis of intravascular coagulation as observed in loxoscelism.
BACKGROUND
The venom of the spider Loxosceles can cause both local and systemic effects including disseminated intravascular coagulation.


OBJECTIVE
The aim of this study was to investigate the effects of the venom of Loxosceles intermedia (L. intermedia) and the purified Sphingomyelinase D (SMaseD) toxin upon the Protein C (PC) natural anticoagulant pathway.


RESULTS
Both the venom and e purified SMaseD reduced the cell surface expression of thrombomodulin (TM) and Endothelial PC Receptor on endothelial cells in culture. The reduction of cell surface expression was caused by cleavage from the cell surface mediated by activation of an endogenous metalloproteinase. Reduction of TM and Endothelial PC Receptor on the surface of these cells resulted in an impaired ability of the cells to assist in the thrombin-induced activation of PC.


CONCLUSIONS
This novel observation gives further insight into the mechanisms of the pathology induced by venom from Loxosceles spiders and may aid the development of a suitable therapy.
van den Berg
C W
CW
Department of Pharmacology, Therapeutics and Toxicology, Wales Heart Research Institute, Cardiff University, Wales College of Medicine, Cardiff, UK. vandenbergcw@cardiff.ac.uk
Gonçalves-de-Andrade
R M
RM
Magnoli
F C
FC
Tambourgi
D V
DV
D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002478:Cells, Cultured; D004211:Disseminated Intravascular Coagulation; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism / Q000633:toxicity*; D011486:Protein C / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013111:Spider Venoms / Q000633:toxicity*; D018180:Thrombomodulin / Q000378:metabolism*
D001779:Blood Coagulation Factors; D011486:Protein C; D011956:Receptors, Cell Surface; D013111:Spider Venoms; D018180:Thrombomodulin; C091963:activated protein C receptor; C055161:loxosceles venom; D010727:Phosphoric Diester Hydrolases; C055160:sphingomyelin phosphodiesterase D; D045726:Metalloproteases