Tityus discrepans scorpion venom activates platelets through GPVI and a novel Src-dependent signaling pathway.

Abstract:

:In humans and other mammals, Tityus discrepans (Td) scorpion envenomation produces a variety of systemic effects including respiratory distress, a generalized inflammatory reaction, modulation of blood pressure, fibrin formation, and platelet activation. For many of these effects, the venom components and underlying mechanisms are not known. In the present study, we demonstrate that Td venom (TdV) stimulates integrin αIIbβ3-dependent aggregation of washed human and mouse platelets downstream of Src kinase activation. The pattern of increase in tyrosine phosphorylation induced by TdV in human platelets is similar to that induced by the collagen receptor GPVI, and includes FcR γ-chain, Syk, and PLC γ 2. Confirmation of GPVI activation by TdV was achieved by expression of human GPVI in chicken DT40 B cells and use of a reporter assay. To our surprise, TdV was able to activate mouse platelets deficient in the GPVI-FcR γ-chain complex through a pathway that was also dependent on Src kinases. TdV therefore activates platelets through GPVI and a second, as yet unidentified Src kinase-dependent pathway.

journal_name

Platelets

journal_title

Platelets

authors

Brazón J,Hughes CE,Mori J,Sevcik C,D'suze G,Watson SP

doi

10.3109/09537104.2010.544343

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

165-72

issue

3

eissn

0953-7104

issn

1369-1635

journal_volume

22

pub_type

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