HEPARINASE ACTIVITY EXPRESSED BY PLATELETS, NEUTROPHILS, AND LYMPHOMA-CELLS RELEASES ACTIVE FIBROBLAST GROWTH-FACTOR FROM EXTRACELLULAR-MATRIX

HEPARINASE ACTIVITY EXPRESSED BY PLATELETS, NEUTROPHILS, AND LYMPHOMA-CELLS RELEASES ACTIVE FIBROBLAST GROWTH-FACTOR FROM EXTRACELLULAR-MATRIX
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DOI:
10.1091/mbc.1.11.833
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发表时间:
1990-10-01
期刊:
CELL REGULATION
影响因子:
--
通讯作者:
VLODAVSKY, I
VLODAVSKY, I
中科院分区:
其他
文献类型:
--
作者:
ISHAIMICHAELI, R;ELDOR, A;VLODAVSKY, I

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将血小板、中性粒细胞和淋巴瘤细胞与牛角膜的后弹力层和培养的角膜内皮细胞产生的细胞外基质(ECM)孵育,导致碱性成纤维细胞生长因子(bFGF)的释放,其刺激3 T3成纤维细胞和血管内皮细胞的增殖。对于储存在德斯密氏膜中的内源性bFGF和被内皮下ECM隔离的外源性bFGF的释放,观察到类似的要求。 释放ECM居民碱性成纤维细胞生长因子的血小板,嗜中性粒细胞,淋巴瘤细胞抑制角叉菜胶λ,但不是蛋白酶抑制剂,与这些细胞表达的乙酰肝素酶活性的抑制。ECM-硫酸乙酰肝素侧链被这种内切-β- D-葡萄糖醛酸酶被认为在细胞侵袭中起重要作用,特别是在血液传播的肿瘤细胞和免疫系统的活化细胞的外渗中。我们建议,乙酰肝素酶和ECM居民碱性成纤维细胞生长因子可以调节细胞反应,以接触其本地环境。乙酰肝素酶介导的活性bFGF从储存在基底膜中的释放提供了在各种正常和病理过程(如伤口愈合、炎症和肿瘤发展)中局部诱导新血管形成的新机制。
Incubation of platelets, neutrophils, and lymphoma cells with Descemet''s membranes of bovine corneas and with the extracellular matrix (ECM) produced by cultured corneal endothelial cells resulted in release of basic fibroblast growth factor (bFGF), which stimulated the proliferation of 3T3 fibroblasts and vascular endothelial cells. Similar requirements were observed for release of endogenous bFGF stored in Descemet''s membrane and of exogenous bFGF sequestered by the subendothelial ECM. Release of ECM-resident bFGF by platelets, neutrophils, and lymphoma cells was inhibited by carrageenan lambda, but not by protease inhibitors, in correlation with the inhibition of heparanase activity expressed by these cells. Degradation of the ECM-heparan sulfate side chains by this endo-.beta.-D-glucuronidase is thought to play an important role in cell invasion, particularly in the extravasation of blood-borne tumor cells and activated cells of the immune system. We propose that both heparanase and ECM-resident bFGF may modulate the cell response to contact with its local environment. Heparanase-mediated release of active bFGF from storage in basement membranes provides a novel mechanism for a localized induction of neovascularization in various normal and pathological processes, such as wound healing, inflammation, and tumor development.