Hauser P, Vaes G
Biochem J. 1978 May 15;172(2):275-84. doi: 10.1042/bj1720275.
When cultivated together with pieces of cartilage biosynthetically labelled with 35S in their proteoglycans, rabbit macrophages, differentiated in vitro from bone-marrow cells, cause the release of soluble 35S-labelled material into the culture medium. This process is inhibited by killing the macrophages or by cycloheximide treatment, and is due to the secretion by the cells of a metal-dependent neutral proteinase capable of degrading cartilage proteoglycan subunits into fragments of high molecular weight. Enzyme activity is optimum at about pH7, and is inhibited by EDTA, o-phenanthroline, cysteine or serum, but not by di-isopropyl phosphorofluoridate nor by 4-hydroxymercuribenzoate. The effect of EDTA is partially reversed by Co2+ or Zn2+ ions. The enzyme is eluted from Sephadex G-150 columns as a single peak of material (apparent mol.wt. 17000) that contains also most of the proteolytic activity exerted by culture media on Azocoll (denatured collagen) or on casein. The possible role of this metalloproteinase in chronic inflammatory processes is discussed, particularly in connection with joint erosions in rheumatoid arthritis.
当与蛋白聚糖中用³⁵S进行生物合成标记的软骨碎片共同培养时，由骨髓细胞体外分化而来的兔巨噬细胞会导致可溶性³⁵S标记物质释放到培养基中。这个过程可通过杀死巨噬细胞或用环己酰亚胺处理来抑制，并且是由于细胞分泌一种金属依赖性中性蛋白酶，该酶能够将软骨蛋白聚糖亚基降解成高分子量片段。酶活性在约pH7时最佳，并且会被乙二胺四乙酸（EDTA）、邻菲罗啉、半胱氨酸或血清抑制，但不会被二异丙基氟磷酸酯或对羟基汞苯甲酸抑制。EDTA的作用可被Co²⁺或Zn²⁺离子部分逆转。该酶从葡聚糖G - 150柱上洗脱时为单一物质峰（表观分子量17000），该峰还包含培养基对偶氮胶原（变性胶原）或酪蛋白发挥的大部分蛋白水解活性。本文讨论了这种金属蛋白酶在慢性炎症过程中的可能作用，特别是与类风湿性关节炎中的关节侵蚀相关的作用。
