Mast cell derived heparin activates the contact system: a link to kinin generation in allergic reactions
Mast cell derived heparin activates the contact system: a link to kinin generation in allergic reactions
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肥大细胞来源的肝素激活接触系统：过敏反应中激肽生成的联系
DOI：
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发表时间：
1997
影响因子：
6.1
通讯作者：
M. Silverberg
中科院分区：
文献类型：
--
作者：
T. Brunnée;S. Reddigari;Y. Shibayama;A. Kaplan;M. Silverberg
当等离子体与带负电荷的人造表面接触时，就会发生接触激活，但目前还没有发现能在体内引发接触激活的物质。我们从一种类似于人类组织型肥大细胞HepPG的小鼠肥大细胞瘤来源细胞系中分离出肥大细胞肝素蛋白多糖（MC‐HepPG）。对该材料和其他糖胺聚糖（GAGs）进行了测试，以证明它们能够加速因子XII和prekallikrein的相互激活以及因子XII的自激活。定量分析表明，MC‐HepPG在重量基础上与葡聚糖硫酸盐一样活跃；猪肠肝素，硫酸皮聚糖。聚硫酸角蛋白和硫酸软骨素C活性较低，其他硫酸酸化多糖基本无活性。MC - HepPG在1:4稀释的血浆中孵育导致高分子量激肽原在因子Xll依赖性反应中完全裂解。上述MC - HepPG依赖性反应均可通过肝素酶I和II预孵育抑制，但肝素酶预处理不能抑制。软骨素酶ABC或丝氨酸蛋白酶抑制剂aPMSF，因此表明肝素蛋白多糖确实起着初始“表面”的作用。采用高效液相色谱凝胶过滤法对蛋白多糖制备过程进行分析。分子量在> ~ 400000 ~ 8000之间的馏分是活性引发剂。从蛋白核上获得的GAG侧链切割前后的色谱对比表明，在分子量69000-17000范围内解离的GAG是最活跃的物种，而不是完整的蛋白多糖。因此，MC - HepPG gag代表了一种生理大分子，其活性与纯化系统中的非生理表面相当，并且具有诱导稀释血浆中接触系统激活的能力。其促进激肽生成的能力与血管周围的细胞和体液炎症反应有关，并为过敏原暴露后观察到的激肽水平升高提供了可能的解释。
Contact activation occurs when plasma comes in contact with negatively charged man‐made surfaces but no substance that initiates contact activation in vivo has been identified. We have isolated a mast cell heparin proteoglycan (MC‐HepPG) from a Furth mouse mastocytoma‐derived cell line that is analogous to human tissue‐type mast cell HepPG. This material and other glycosaminoglycans (GAGs) were tested for their ability to accelerate the reciprocal activation of factor XII and prekallikrein and the autoactivation of factor XII. Quantitative analysis showed the MC‐HepPG to be as active as dextran sulfate on a weight basis; hog intestine heparin, dermatan sulfate. keratan polysulfate and chondroitin sulfate C were less active, other sulfated polysaccharides were essentially inactive. Incubation of MC‐HepPG in 1:4 diluted plasma resulted in complete cleavage of high molecular weight kininogen in a factor Xll‐dependent reaction. All of the MC‐HepPG dependent reactions described above were inhibited by preincubation of MC‐HepPG with heparinase I and II but not by pretreatment with heparitinase. chondroitinase ABC or the serine protease inhibitor aPMSF thus indicating that heparin proteoglycan is indeed acting as an initiating ‘surface’. We analysed the proteoglycan preparation by HPLC gel filtration. Fractions spanning a molecular weight range of > 400000–8000 were active initiators. Comparison of the chromatograms obtained before and after cleavage of GAG side chains from the protein core suggested that dissociated GAGs in the MW range 69000–17000 are the most active species rather than the complete proteoglycan. MC‐HepPG GAGs therefore represent a physiologic macromolecule with activity comparable to non‐physiological surfaces in a purified system and with the capability to induce activation of the contact system in diluted plasma. Its ability to promote kinin generation links cellular and humoral inflammatory responses in the perivasculature and provides a possible explanation for the elevated kinin levels observed after allergen exposure.
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人类哈格曼因子（因子 XII）的活化形式和酶原形式的酶活性。
影响因子：
20.3
作者：
Silverberg,M;Kaplan,AP
通讯作者：
Kaplan,AP
影响因子：
2.9
作者：
LINHARDT, RJ;TURNBULL, JE;GALLAGHER, JT
通讯作者：
GALLAGHER, JT
人类凝血因子 XII（哈格曼因子）的硫脂苷依赖性自动激活。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Tans,G;Rosing,J;Griffin,JH
通讯作者：
Griffin,JH
源自 Furth 鼠肥大细胞瘤的稳定产生肝素的细胞系。
DOI：
10.1073/pnas.89.23.11327
发表时间：
1992
影响因子：
11.1
作者：
Montgomery,RI;Lidholt,K;Flay,NW;Liang,J;Vertel,B;Lindahl,U;Esko,JD
通讯作者：
Esko,JD
大鼠肥大细胞肝素蛋白多糖的氧化降解。
DOI：
10.1042/bj2720051
发表时间：
1990
期刊：
The Biochemical journal
影响因子：
--
作者：
Metcalfe,DD;Thompson,HL;Klebanoff,SJ;HendersonJr,WR
通讯作者：
HendersonJr,WR