Effect of the snake venom component crotamine on lymphatic endothelial cell responses and lymph transport

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2022-06-11 DOI:10.1111/micc.12775

Hongjiang Si, Chunhiu Yin, Wei Wang, Peter Davies, Elda Sanchez, Montamas Suntravat, David Zawieja, Walter Cromer

{"title":"Effect of the snake venom component crotamine on lymphatic endothelial cell responses and lymph transport","authors":"Hongjiang Si, Chunhiu Yin, Wei Wang, Peter Davies, Elda Sanchez, Montamas Suntravat, David Zawieja, Walter Cromer","doi":"10.1111/micc.12775","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>The pathology of snake envenomation is closely tied to the severity of edema in the tissue surrounding the area of the bite. Elucidating the mechanisms that promote the development of such severe edema is critical to a better understanding of how to treat this life-threatening injury. We focused on one of the most abundant venom components in North American viper venom, crotamine, and the effects it has on the cells and function of the lymphatic system.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We used RT-PCR to identify the location and relative abundance of crotamine's cellular targets (Kvα channels) within the tissues and cells of the lymphatic system. We used calcium flux, nitrate production, and cell morphometry to determine the effects of crotamine on lymphatic endothelial cells. We used tracer transport, node morphometry, and node deposition to determine the effects of crotamine on lymph transport in vivo.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We found that genes that encode targets of crotamine are highly present in lymphatic tissues and cells and that there is a differential distribution of those genes that correlates with phasic contractile activity. We found that crotamine potentiates calcium flux in human dermal lymphatic endothelial cells in response to stimulation with histamine and sheer stress (but not alone) and that it alters the production of nitric oxide in response to shear as well as changes the level of F-actin polymerization of those same cells. Crotamine alters lymphatic transport of large molecular weight tracers to local lymph nodes and is deposited within the node mostly in the immediate subcapsular region.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This evidence suggests that snake venom components may have an impact on the function of the lymphatic system. This needs to be studied in greater detail as there are numerous venom components that may have effects on aspects of the lymphatic system. This would not only provide basic information on the pathobiology of snakebite but also provide targets for improved therapeutics to treat snakebite.</p>\n </section>\n </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2022-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850291/pdf/nihms-1858558.pdf","citationCount":"5","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microcirculation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/micc.12775","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 5

Abstract

Objective

The pathology of snake envenomation is closely tied to the severity of edema in the tissue surrounding the area of the bite. Elucidating the mechanisms that promote the development of such severe edema is critical to a better understanding of how to treat this life-threatening injury. We focused on one of the most abundant venom components in North American viper venom, crotamine, and the effects it has on the cells and function of the lymphatic system.

Methods

We used RT-PCR to identify the location and relative abundance of crotamine's cellular targets (Kvα channels) within the tissues and cells of the lymphatic system. We used calcium flux, nitrate production, and cell morphometry to determine the effects of crotamine on lymphatic endothelial cells. We used tracer transport, node morphometry, and node deposition to determine the effects of crotamine on lymph transport in vivo.

Results

We found that genes that encode targets of crotamine are highly present in lymphatic tissues and cells and that there is a differential distribution of those genes that correlates with phasic contractile activity. We found that crotamine potentiates calcium flux in human dermal lymphatic endothelial cells in response to stimulation with histamine and sheer stress (but not alone) and that it alters the production of nitric oxide in response to shear as well as changes the level of F-actin polymerization of those same cells. Crotamine alters lymphatic transport of large molecular weight tracers to local lymph nodes and is deposited within the node mostly in the immediate subcapsular region.

Conclusion

This evidence suggests that snake venom components may have an impact on the function of the lymphatic system. This needs to be studied in greater detail as there are numerous venom components that may have effects on aspects of the lymphatic system. This would not only provide basic information on the pathobiology of snakebite but also provide targets for improved therapeutics to treat snakebite.

查看原文本刊更多论文

蛇毒成分克罗胺对淋巴内皮细胞反应和淋巴运输的影响

目的蛇中毒的病理与被咬部位周围组织水肿的严重程度密切相关。阐明促进这种严重水肿发展的机制对于更好地理解如何治疗这种危及生命的损伤至关重要。我们专注于北美毒蛇毒液中最丰富的毒液成分之一，克罗胺，以及它对淋巴系统细胞和功能的影响。方法利用RT-PCR技术鉴定了克罗米胺的细胞靶点(Kvα通道)在淋巴系统组织和细胞中的位置和相对丰度。我们使用钙通量、硝酸盐生成和细胞形态测定法来确定克罗米胺对淋巴内皮细胞的影响。我们使用示踪剂运输、淋巴结形态测定和淋巴结沉积来确定克罗米胺对体内淋巴运输的影响。结果我们发现，在淋巴组织和细胞中，编码克罗米胺靶标的基因大量存在，并且这些基因与相收缩活性相关的分布存在差异。我们发现，在组胺和纯应激刺激下(但不是单独的)，克罗米胺增强了人真皮淋巴内皮细胞中的钙通量，并改变了对剪切反应的一氧化氮的产生，以及改变了这些细胞的f -肌动蛋白聚合水平。克罗米胺改变大分子量示踪剂到局部淋巴结的淋巴运输，并在淋巴结内沉积，主要在紧邻的包膜下区域。结论蛇毒成分可能对淋巴系统功能有影响。这需要更详细地研究，因为有许多毒液成分可能对淋巴系统的各个方面产生影响。这不仅为蛇咬伤的病理生物学提供了基本信息，而且为改进蛇咬伤的治疗方法提供了靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.