Regulation of extracellular matrix structure as a biological response to chemical stimuli and irradiation

肝素酶最初被鉴定为一种分解硫酸乙酰肝素蛋白多糖的内切β-葡萄糖醛酸酶，该酶在肿瘤生物学领域的病理作用被广泛研究。在这项研究中，我们研究了肝素酶在免疫系统中的功能相关性以及对化学刺激和辐射的生物反应。肝素酶参与了单核细胞对基底膜的降解。分子在细胞表面的封顶和随后在前沿的重新分布是导致降解的原因。制备了一系列抗小鼠乙酰肝素酶的单抗，用于检测乙酰肝素酶在细胞内的分布。乙酰肝素酶在颗粒中积聚在皮肤肥大细胞和炎症微血管中的中性粒细胞中。研究肝素酶在肝素加工和颗粒功能调节中的作用。将乙酰肝素酶基因或重组蛋白导入MST肥大细胞瘤细胞后，活性乙酰肝素酶定位于颗粒。在这些改良的MST细胞中，颗粒肝素被切割成较小的分子尺寸，颗粒酶的活性似乎受到低分子肝素的调节。肝素酶介导的硫酸肝素和肝素的裂解可能调节免疫系统中细胞功能所必需的过程，并在很大程度上参与对化学刺激和辐射的生物反应。

Heparanase was originally identified as an endo-beta-glucuronidase which cleaves heparan sulfate proteoglycan, and the enzyme' s pathological roles were extensively investigated in the field of cancer biology. In the present study, we examined functional relevance of heparanase in the immune system and biological responses to chemical stimuli and irradiation. Heparanase is involved in degradation of the basement membranes by monocytes. Capping of the molecule on the cell surface and subsequent redistribution at the leading edge are responsible for the degradation. A series of anti-mouse heparanase monoclonal antibodies were established and used to examine the intracellular distribution of the enzyme. Heparanase accumulation in the granules was detected in skin mast cells and in neutrophils in the inflamed microvasculature. Involvement of heparanase in heparin processing and modulation of granular function was examined. When heparanase gene or recombinant proteins were incorporated into MST mastcytoma cells, active heparanase was localized to the granules. In these modified MST cells, granular heparin was cleaved into a smaller molecular size and activity of granular enzymes seemed to be modulated by the low-molecular-weight heparin. Heparanase-mediated cleavage of heparan sulfate and heparin is likely to regulate processes essential to the functions of cells in the immune system and there by greatly involved in biological responses to chemical stimuli and irradiation.