Welgus H G, Campbell E J, Bar-Shavit Z, Senior R M, Teitelbaum S L
J Clin Invest. 1985 Jul;76(1):219-24. doi: 10.1172/JCI111949.
Human macrophages have been implicated in connective tissue remodeling; however, little is known about their direct effects upon collagen degradation. We now report that human alveolar macrophages in culture produced both a collagenase and a collagenase inhibitor. The collagenase was secreted in latent form and could be activated by exposure to trypsin. Collagenase production could be increased three- to fourfold by incubating the cells with lipopolysaccharide, but synthesis was largely unaffected by exposure to phorbol myristate acetate. By several criteria, macrophage collagenase was the same as the collagenase secreted by human skin fibroblasts: (a) they were antigenically indistinguishable in double immunodiffusion; (b) both degraded type III collagen preferentially to type I, had little activity against type II collagen, and none against types IV and V, and (c) their affinity for susceptible collagens was equivalent, Michaelis constant = 1-2 microM. Collagenase inhibitory activity was also present in the macrophage-conditioned medium, and was accounted for by an antigen that showed immunologic and functional identity with the collagenase inhibitor secreted by human skin fibroblasts. The amount of inhibitor released by unstimulated cells, approximately 100 ng/10(6) cells per 24 h, was substantially augmented by both phorbol and lipopolysaccharide, although considerable variability in response to these agents was observed between macrophage populations derived from different subjects. As negligible quantities of collagenase or collagenase inhibitor were detectable intracellularly, it appeared that both proteins were secreted rapidly after synthesis. Thus, human macrophages have the capacity to modulate collagen degradation directly by production of collagenase and collagenase inhibitor.
人类巨噬细胞与结缔组织重塑有关；然而，关于它们对胶原蛋白降解的直接作用却知之甚少。我们现在报告，培养的人类肺泡巨噬细胞可产生一种胶原酶和一种胶原酶抑制剂。胶原酶以潜伏形式分泌，可通过胰蛋白酶激活。用脂多糖孵育细胞可使胶原酶产量增加三到四倍，但佛波酯肉豆蔻酸酯乙酸盐处理对其合成影响不大。根据多项标准，巨噬细胞胶原酶与人类皮肤成纤维细胞分泌的胶原酶相同：（a）在双向免疫扩散中它们的抗原性无法区分；（b）二者均优先降解III型胶原蛋白而非I型，对II型胶原蛋白几乎无活性，对IV型和V型胶原蛋白则无活性，且（c）它们对敏感胶原蛋白的亲和力相当，米氏常数 = 1 - 2 microM。巨噬细胞条件培养基中也存在胶原酶抑制活性，其由一种抗原引起，该抗原与人类皮肤成纤维细胞分泌的胶原酶抑制剂在免疫学和功能上具有一致性。未受刺激的细胞每24小时释放的抑制剂约为100 ng/10⁶个细胞，佛波酯和脂多糖均可使其显著增加，尽管不同受试者来源的巨噬细胞群体对这些试剂的反应存在相当大的差异。由于细胞内可检测到的胶原酶或胶原酶抑制剂数量极少，似乎这两种蛋白质在合成后迅速分泌。因此，人类巨噬细胞有能力通过产生胶原酶和胶原酶抑制剂直接调节胶原蛋白降解。
