Induction of microvascular leakage and histamine release by promutoxin, an Arg49 phospholipase A2

Wei, Ji‐Fu; Wei, Xiao-Long; Mo, Ya-Zhen; He, Shaoheng

doi:10.1016/j.toxicon.2009.12.016

Cited by 11 publications

(6 citation statements)

References 41 publications

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“…Numerous studies have reported on the histamine-releasing capabilities of various snake venoms [ 219 , 224 , 225 , 226 , 227 ], based upon their capacity to degranulate mast cells [ 228 , 229 , 230 ]; however, to the best of our knowledge, histamine has been reported as an actual component of a snake venom only once ( Bitis gabonica ) [ 231 ]. Recently, Mamede et al [ 232 ] reported that the inflammatory reaction caused by Bothrops moojeni venom is mediated by eicosanoids, histamine, nitric oxide, and bradykinin, principally due to the action of phospholipases, metalloproteases, and serine proteases.…”

Section: Resultsmentioning

confidence: 99%

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Villar‐Briones

Aird

2018

Toxins

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Small metabolites and peptides in 17 snake venoms (Elapidae, Viperinae, and Crotalinae), were quantified using liquid chromatography-mass spectrometry. Each venom contains >900 metabolites and peptides. Many small organic compounds are present at levels that are probably significant in prey envenomation, given that their known pharmacologies are consistent with snake envenomation strategies. Metabolites included purine nucleosides and their bases, neurotransmitters, neuromodulators, guanidino compounds, carboxylic acids, amines, mono- and disaccharides, and amino acids. Peptides of 2–15 amino acids are also present in significant quantities, particularly in crotaline and viperine venoms. Some constituents are specific to individual taxa, while others are broadly distributed. Some of the latter appear to support high anabolic activity in the gland, rather than having toxic functions. Overall, the most abundant organic metabolite was citric acid, owing to its predominance in viperine and crotaline venoms, where it chelates divalent cations to prevent venom degradation by venom metalloproteases and damage to glandular tissue by phospholipases. However, in terms of their concentrations in individual venoms, adenosine, adenine, were most abundant, owing to their high titers in Dendroaspis polylepis venom, although hypoxanthine, guanosine, inosine, and guanine all numbered among the 50 most abundant organic constituents. A purine not previously reported in venoms, ethyl adenosine carboxylate, was discovered in D. polylepis venom, where it probably contributes to the profound hypotension caused by this venom. Acetylcholine was present in significant quantities only in this highly excitotoxic venom, while 4-guanidinobutyric acid and 5-guanidino-2-oxopentanoic acid were present in all venoms.

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Section: Resultsmentioning

confidence: 99%

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Villar‐Briones

Aird

2018

Toxins

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“…Inhibition of 71.3 and 92.6% promutoxin-induced mast-cell accumulation by cyproheptadine, a histamine/5-HT antagonist, and terfenadine a selective histamine-H 1 -receptor antagonist, implies that histamine is likely to be involved in the above event through its H 1 receptor. Indeed, we have found previously that promutoxin can activate mast cells to release histamine [24] and anticipate herein that released histamine then elicits mast-cell migration. The fact that terfenadine inhibited promutoxin-provoked mast-cell recruitment to a greater extent than cyproheptadine further implies the selectivity of histamine receptor involved.…”

Section: Discussionmentioning

confidence: 59%

“…The purity of the PLA 2 was at least 98% as assessed by SDS-PAGE, HPLC, and mass spectrometry analysis [24]. …”

Section: Resultsmentioning

confidence: 99%

“…The observation supports our previous finding that N49 PLA 2 , another minor subgroup of snake-venom group II PLA 2 s [23] can induce mast-cell accumulation. Obviously, promutoxin does not induce mast-cell accumulation in a concentration-dependent manner [24]. We previously found that promutoxin could activate mast-cells.…”

Section: Discussionmentioning

confidence: 99%

“…Several snake-venom PLA 2 s were reported to be able to activate the rat mast cells and to induce microvascular leakage and inflammatory-cell accumulation at the sites of inflammation [15–20]. Our previous studies showed that TM-N49, an N49 PLA 2 purified from Protobothrops mucrosquamatus venom, induces skin edema and mast-cell activation and accumulation [23], and promutoxin, an R49 PLA 2 purified from the same snake, can activate mast cells and induce skin edema [24]. Both TM-N49 and promutoxin are devoid of catalytic activity and are thought to contribute to Protobothrops mucrosquamatus venom toxicity [5, 8].…”

Section: Introductionmentioning

confidence: 99%

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Induction of Mast-Cell Accumulation by Promutoxin, an Arg-49 PhospholipaseA2

Wei

et al. 2013

BioMed Research International

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Local inflammation is a prominent characteristic of snakebite wound, and snake-venom phospholipase A2s (PLA2s) are some of the main component that contribute to accumulation of inflammatory cells. However, the action of an R49 PLA2s, promutoxin from Protobothrops mucrosquamatus venom, on mast-cell accumulation has not been previously examined. Using a mouse peritoneal model, we found that promutoxin can induce approximately-6-fold increase in mast-cell accumulation, and the response lasts at least for 16 h. The promutoxin-induced mast cell accumulation was inhibited by cyproheptadine, terfenadine, and Ginkgolide B, indicating that histamine and platelet-activating factor (PAF) is likely to contribute to the mast-cells accumulation. Preinjection of antibodies against adhesion molecules ICAM-1, CD18, CD11a, and L-selectin showed that ICAM-1, and CD18, CD11a are key adhesion molecules of promutoxin-induced mast-cell accumulation. In conclusion, promutoxin can induce accumulation of mast cells, which may contribute to snake-venom wound.

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