Abstract
Envenomation by Loxosceles spider is characterized by the development of dermonecrosis. In previous studies, we have demonstrated that increased expression/secretion of matrix metalloproteinases 2 and 9, induced by Loxosceles intermedia venom Class 2 SMases D (the main toxin in the spider venom), contribute to the development of cutaneous loxoscelism. In the present study we show that the more potent venom containing the Class 1 SMase D from Loxosceles laeta, in addition to increasing the expression/secretion of MMP2 and MMP9, also stimulates the expression of MMP7 (Matrilysin-1), which was associated with keratinocyte cell death. Tetracycline, a matrix metalloproteinase inhibitor, prevented cell death and reduced MMPs expression. Considering that L. laeta venom is more potent at inducing dermonecrosis than L. intermedia venom, our results suggest that MMP7 may play an important role in the severity of dermonecrosis induced by L. laeta spider venom SMase D. In addition, the inhibition of MMPs by e.g. tetracyclines may be considered for the treatment of the cutaneous loxoscelism.
Highlights
The spiders of the genus Loxosceles, Sicariidae family, commonly known in the Americas as brown or recluse spiders, can induce serious local and systemic effects in humans upon envenomation [1]
In the rabbit model of cutaneous loxoscelism, as well as in human keratinocytes cultures, we previously showed that L. intermedia Class 2 SMases D induced an increase in the expression of matrix metalloproteinases- 2 and 9 (MMP2, MMP9), which likely contribute to the pathology of cutaneous loxoscelism [16, 17]
We previously reported that L. intermedia venom and it’s class 2 sphingomyelinase D (SMase D), induced cell death by apoptosis in the human keratinocyte cell line HaCaT [17]
Summary
The spiders of the genus Loxosceles, Sicariidae family, commonly known in the Americas as brown or recluse spiders, can induce serious local and systemic effects in humans upon envenomation [1]. Loxosceles envenomation can locally result in extensive tissue destruction and chronic ulcer formation which take many months to heal [2,3,4]. Complement mediated hemolysis, disseminated intravascular coagulation, shock and renal impairment are rare systemic reactions, but are the main causes of death associated with Loxosceles envenomation. Substrates of SMases D include sphingomyelin and lysophosphatidylcholine, hydrolysis of which results in the release of choline and formation of ceramide-1-phosphate and lysophosphatidic acid, both of which have the potency to activate cells [5,6,7,8,9].
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