Histamine Regulates Binding of Cross-Linked Fibrinogen to Endothelium: Role of Histaminylation in Vascular Biology

组织谷氨酰胺转胺酶 组胺 纤维蛋白 纤维蛋白原 生物化学 细胞外 细胞生物学 细胞外基质 因子XIIIa 血管平滑肌 化学 内皮干细胞 生物 免疫学 体外 内分泌学 平滑肌
作者
Thung‐S. Lai,Charles S. Greenberg
出处
期刊:Blood [American Society of Hematology]
卷期号:120 (21): 3304-3304
标识
DOI:10.1182/blood.v120.21.3304.3304
摘要

Abstract Abstract 3304 Recent studies have demonstrated that a wide variety of biogenic amines can be covalently cross-linked to intracellular and extracellular proteins. This “aminylation” reaction regulates several important reactions in vascular biology. Serotinylation of small GTPases recently was shown to regulate cell signaling events, platelet activation and promote vascular smooth muscle cell proliferation. The role of extracellular crosslinking of biogenic amines to plasma and extracellular matrix proteins is not well established and could play a role in altering transglutaminase reactions in vascular tissue. Tissue translutaminase (TGM-2) crosslinking of the a-C domain of fibrinogen has been shown to promote clustering of RGD domains, enhance binding of the cross-linked polymers to endothelial cells and promote cell adhesion. While Factor XIIIa prefers to crosslink fibrin, the TGM-2 molecule which is abundantly expressed by erythrocytes, endothelial and vascular smooth muscle cells does not show any preference for fibrin compared to fibrinogen. TGM-2 is a sulfhydryl rich calcium-dependent enzyme that could cross-link a variety of biogenic amines to fibrinogen. We investigated the preference of TGM-2 crosslinking of biogenic amines to fibrinogen in vitro and determined whether the crosslinking would modify the transglutaminase-dependent binding of fibrinogen to endothelial cells. We found histamine was the most effective primary amine inhibitor of the TGM2-mediated cross-linking reaction (Histamine > putrescine >>> serotonin, dopamine, noradrenaline). 1.25 mM histamine inhibited > 75% TGM2-mediated fibrinogen and fibrin cross-linking. The ability of TGM-2 crosslinked fibrinogen complexes to bind to confluent human umbilical vascular endothelial cell (HUVEC) was also studied. Free [125I]-fibrinogen bound to endothelial cells with low affinity, however the binding was increased ∼7 fold when fibrinogen was cross-linked by TGM2. The increase in crosslinked fibrinogen binding was dependent on TGM2 and Ca+2 concentration. Unlabeled crosslinked fibrinogen inhibited the binding by more than 85%. In contrast, unlabeled fibrinogen actually enhanced the binding 1.7 fold suggesting that fibrinogen and cross-linked fibrinogen formed multivalent complexes with cross-linked fibrinogens on the endothelial cell surface. When bound complex were eluted from HUVEC cells after binding experiments, >95% of bound materials were extensively crosslinked and could not enter a 5–15% polyacrylamide gel. In contrast, no high molecular weight material was eluted when non-crosslinked fibrinogen was used in the binding experiments. When fibrinogen was cross-linked in the presence of 8 to 500 micromolar of histamine, the binding was inhibited by ∼75 to 90 %, respectively. In summary, TGM-2 cross-linked fibrinogen showed enhanced binding to endothelial cells as previously reported for purified aC domains of fibrinogen. The binding of fibrinogen to endothelial cells is known to enhance endothelial cell adhesion and leukocyte transmigration, reactions that are involved in wound healing, angiogenesis and inflammation. The TGM-2 crosslinked fibrinogen/fibrinogen complexes may serve as proinflammatory, prothrombotic and proangiogenic factors in vivo. Histaminylation of fibrinogen by TGM-2 could provide a mechanism to regulate these vascular events. Fibrinogen could also serve to control local histamine function as only free histamine can bind to histamine receptors. Transglutaminase mediated histaminylation of fibrinogen could have multiple effects on acute and chronic inflammatory reactions. Disclosures: No relevant conflicts of interest to declare.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
1秒前
圆芋头完成签到 ,获得积分10
1秒前
3秒前
yanfangliu发布了新的文献求助10
4秒前
俭朴白猫完成签到,获得积分10
4秒前
Strike发布了新的文献求助10
6秒前
田様应助xixi采纳,获得10
6秒前
搜集达人应助xixi采纳,获得10
7秒前
SciGPT应助可耐的含羞草采纳,获得10
8秒前
头发乱了发布了新的文献求助10
9秒前
9秒前
奶盖完成签到 ,获得积分10
10秒前
酷波er应助111采纳,获得10
11秒前
科研通AI2S应助hkh采纳,获得10
12秒前
13秒前
13秒前
小蘑菇应助重要的道之采纳,获得20
13秒前
该房地产个人的完成签到,获得积分10
14秒前
华仔应助健康的绮晴采纳,获得10
15秒前
16秒前
杨旭发布了新的文献求助10
18秒前
Samlion完成签到,获得积分10
18秒前
科研通AI2S应助Strike采纳,获得50
18秒前
19秒前
19秒前
FAN发布了新的文献求助10
19秒前
传奇3应助seaya采纳,获得10
20秒前
22秒前
viauue9完成签到,获得积分10
22秒前
yangmingyu发布了新的文献求助10
22秒前
22秒前
p13508397190完成签到,获得积分10
23秒前
今后应助jjy采纳,获得10
24秒前
头发乱了完成签到,获得积分10
25秒前
26秒前
葳葳完成签到,获得积分10
27秒前
yanfangliu完成签到,获得积分10
27秒前
xixi发布了新的文献求助10
28秒前
28秒前
高分求助中
Evolution 10000
Sustainability in Tides Chemistry 2800
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
Diagnostic immunohistochemistry : theranostic and genomic applications 6th Edition 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3155790
求助须知:如何正确求助?哪些是违规求助? 2807042
关于积分的说明 7871703
捐赠科研通 2465404
什么是DOI,文献DOI怎么找? 1312221
科研通“疑难数据库(出版商)”最低求助积分说明 629958
版权声明 601905