Structurally Robust and Functionally Highly Versatile—C-Type Lectin (-Related) Proteins in Snake Venoms

Eble, Johannes A.

doi:10.3390/toxins11030136

Cited by 41 publications

(27 citation statements)

References 213 publications

(344 reference statements)

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“…Their inhibitory mechanism and efficacy on RGD-dependent integrins have been derived from snake venom disintegrins (Huang et al, 2016;Estevao-Costa et al, 2018). Another toxin class from snake venoms, the C-type lectin-related proteins, are very efficient inhibitors specifically directed to the receptors for collagen and vWF (Eble, 2019).…”

Section: Perspectives For Translation Into Clinical Treatment Strategiesmentioning

confidence: 99%

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

Obermann

Brockhaus

Eble

2021

Front. Cell Dev. Biol.

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Although platelets and the coagulation factors are components of the blood system, they become part of and contribute to the tumor microenvironment (TME) not only within a solid tumor mass, but also within a hematogenous micrometastasis on its way through the blood stream to the metastatic niche. The latter basically consists of blood-borne cancer cells which are in close association with platelets. At the site of the primary tumor, the blood components reach the TME via leaky blood vessels, whose permeability is increased by tumor-secreted growth factors, by incomplete angiogenic sprouts or by vasculogenic mimicry (VM) vessels. As a consequence, platelets reach the primary tumor via several cell adhesion molecules (CAMs). Moreover, clotting factor VII from the blood associates with tissue factor (TF) that is abundantly expressed on cancer cells. This extrinsic tenase complex turns on the coagulation cascade, which encompasses the activation of thrombin and conversion of soluble fibrinogen into insoluble fibrin. The presence of platelets and their release of growth factors, as well as fibrin deposition changes the TME of a solid tumor mass substantially, thereby promoting tumor progression. Disseminating cancer cells that circulate in the blood stream also recruit platelets, primarily by direct cell-cell interactions via different receptor-counterreceptor pairs and indirectly by fibrin, which bridges the two cell types via different integrin receptors. These tumor cell-platelet aggregates are hematogenous micrometastases, in which platelets and fibrin constitute a particular TME in favor of the cancer cells. Even at the distant site of settlement, the accompanying platelets help the tumor cell to attach and to grow into metastases. Understanding the close liaison of cancer cells with platelets and coagulation factors that change the TME during tumor progression and spreading will help to curb different steps of the metastatic cascade and may help to reduce tumor-induced thrombosis.

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Section: Perspectives For Translation Into Clinical Treatment Strategiesmentioning

confidence: 99%

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

Obermann

Brockhaus

Eble

2021

Front. Cell Dev. Biol.

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“…These proteins exhibit the C-type lectin domain (CTLD) but differ from it in a long loop that either contributes to the sugar-binding site or is expanded into a loop-swapping heterodimerization domain between two CLRP subunits. SV-CLRPs connect with a multitude of molecules implicated in hemostasis that are present on endothelial cells, coagulation factors, and receptors of platelets, having a role in thrombus formation and inflammation (150).…”

Section: Inflammation Induced By Viper Snake Venommentioning

confidence: 99%

Inflammation Induced by Platelet-Activating Viperid Snake Venoms: Perspectives on Thromboinflammation

et al. 2019

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Envenomation by viperid snakes is characterized by systemic thrombotic syndrome and prominent local inflammation. To date, the mechanisms underlying inflammation and blood coagulation induced by Viperidae venoms have been viewed as distinct processes. However, studies on the mechanisms involved in these processes have revealed several factors and signaling molecules that simultaneously act in both the innate immune and hemostatic systems, suggesting an overlap between both systems during viper envenomation. Moreover, distinct classes of venom toxins involved in these effects have also been identified. However, the interplay between inflammation and hemostatic alterations, referred as to thromboinflammation, has never been addressed in the investigation of viper envenomation. Considering that platelets are important targets of viper snake venoms and are critical for the process of thromboinflammation, in this review, we summarize the inflammatory effects and mechanisms induced by viper snake venoms, particularly from the Bothrops genus, which strongly activate platelet functions and highlight selected venom components (metalloproteases and C-type lectins) that both stimulate platelet functions and exhibit pro-inflammatory activities, thus providing insights into the possible role(s) of thromboinflammation in viper envenomation.

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“…However, CTLs show an indiscriminate ligand spectrum, targeting clotting factors and several receptors on platelets, endothelial cells, and immune cells. This results in a wide range of pharmacological activities, acting in hemostasis and inflammation ( 84 ). There are no studies that disclose the isolation and characterization of this protein class from C. d. ruruima .…”

Section: Crotalus Durissus Ruruima: Venom Compositionmentioning

confidence: 99%

Crotalus Durissus Ruruima: Current Knowledge on Natural History, Medical Importance, and Clinical Toxinology

Pucca

Bernarde

Rocha³

et al. 2021

Front. Immunol.

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Crotalus durissus ruruima is a rattlesnake subspecies mainly found in Roraima, the northernmost state of Brazil. Envenomings caused by this subspecies lead to severe clinical manifestations (e.g. respiratory muscle paralysis, rhabdomyolysis, and acute renal failure) that can lead to the victim’s death. In this review, we comprehensively describe C. d. ruruima biology and the challenges this subspecies poses for human health, including morphology, distribution, epidemiology, venom cocktail, clinical envenoming, and the current and future specific treatment of envenomings by this snake. Moreover, this review presents maps of the distribution of the snake subspecies and evidence that this species is responsible for some of the most severe envenomings in the country and causes the highest lethality rates. Finally, we also discuss the efficacy of the Brazilian horse-derived antivenoms to treat C. d. ruruima envenomings in Roraima state.

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Structurally Robust and Functionally Highly Versatile—C-Type Lectin (-Related) Proteins in Snake Venoms

Cited by 41 publications

References 213 publications

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

Inflammation Induced by Platelet-Activating Viperid Snake Venoms: Perspectives on Thromboinflammation

Crotalus Durissus Ruruima: Current Knowledge on Natural History, Medical Importance, and Clinical Toxinology

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