KERATINOCYTE NEUTRAL SECRETORY PROTEASES AND INHIBITORS

中性分泌的功能及其调节的研究 角质形成细胞介导的间质胶原和蛋白水解酶 基底膜降解。(1)活的角质形成细胞 在培养中降解间质I型和III型胶原纤维 被测量的和特定的和协调的作用的组成的蛋白酶 胶原酶复合体：一个65K胶原酶，一个110K明胶酶，两个(70K 和48K)纤溶酶原激活剂和外源性纤溶酶原 通过免疫抑制。将搜索其他组件 原胶原酶特异性激活剂等胶原酶裂解复合体 和纤溶酶原激活物以及血浆和 内源性分泌性蛋白水解酶抑制剂，包括表皮抑制物 对纤溶系统和胶原蛋白溶解系统进行分析。(2) 角质细胞降解完整基底膜的能力将是 调查过了。IV型胶原、层粘连蛋白、 纤维连接蛋白和硫酸乙酰肝素蛋白多糖降解系统 IV型胶原降解蛋白的鉴定及其特异性功能的研究 蛋白水解酶系统将通过特异性免疫抑制进行分析。(3) 蛋白分解能力的表达作为基底细胞激活的函数 将会被调查。(A)分泌物之间的反向关系 锚定诱导的特异性蛋白水解酶与终末分化 体外剥离将建立并分布和定位 在贴壁原代外植体和克隆体中的分泌细胞 菌落将与分化标记的菌落相关。(B) 切除诱导活化的基底细胞合成蛋白水解酶 体内损伤将通过免疫荧光进行研究，并与 愈合过程中的迁移、汇流和分层。(C) 黄曲霉毒素对间质胶原和基底膜降解的影响 调节活化和分化细胞表达的药物 如维甲酸、糖皮质激素、炎性物质和环状 将对核苷酸进行分析。

A study is proprosed of the function and regulation of neutral secretory proteases in keratinocyte-mediated interstitial collagen and basement-membrane degradation. (1) The ability of live keratinocytes to degrade interstitial type I and III collagen fibrils in culture will be measured and the specific and coordinate role of the component proteases of the collagenolytic complex: a 65K collagenase, a 110K gelatinase, two (70K and 48K) plasminogen activators and exogenous plasminogen will be analyzed by immune-inhibition. A search will be made for additional components of the collagenolytic complex such as specific activators of procollagenase and plasminogen proactivators and the regulatory role of plasma and endogenous secretory protease inhibitors, including epidermal inhibitors of the fibrinolytic and collagenolytic systems, will be analyzed. (2) The ability of keratinoyctes to degrade intact basement membranes will be investigated. The component proteases of the type IV collagen, laminin, fibronectin and heparan sulfate proteoglycan degrading systems will be identified and the specific function of the type IV-collagen-degrading protease system will be analyzed by specific immune inhibition. (3) The expression of proteolytic competence as a function of basal cell activation will be investigated. (a) The inverse relationship between secretion of specific proteases and terminal differentiation induced by anchorage deprivation in vitro will be established and the distribution and position of secretor cells in surface-attached primary explants and in clonal colonies will be correlated with that of differentiation markers. (b) The synthesis of proteases by activated basal cells induced by excision wounding in vivo will be studied by immunofluorescence and correlated with migration, confluence and stratification during the healing process. (c) The effect on interstitial collagen and basement membrane degradation of agents which modulate expression of activated and differentiated cellular states such as retinoids, glucocorticoids, inflammatory agents and cyclic nucleotides will be analyzed.