Spitznagel J K, Modrzakowski M C, Pryzwansky K B, MacRae E K
Environ Health Perspect. 1980 Apr;35:29-38. doi: 10.1289/ehp.803529.
Tissue proteolytic enzymes are currently believed to be critical to the pathogenesis of panacinar emphysema. Polymorphonuclear leukocytes (Polys) have several enzymes including elastase and cathepsin G in their azurophil granules. They have collagenase in their specific granules. We have found that this collagenase is doubly latent. It has the lysosomal type of latency that depends on the impermeability of the unit membrane that surrounds each specific granule. In addition it has a latency that is converted to activity by proteolytic enzymes. The cathepsin G of the azurophil granule is a potent activator of this latent collagenase once the collagenase is released from its membrane dependent latency. Thus latency of enzymes, the nature of the latency and accessibility of the latent enzymes to activating mechanisms must all be taken into account in any analysis of their contribution to pathogenesis of local lung disease. Equally important is that fact that polys are not a prominent cellular component of normal lung. Polys must be attracted to the lung by chemotactic peptides. These peptides must be released by the interaction of inflammatory stimuli, such as smoke particles, with complement components or they must be provided by other sources. The hypothesis that lung damage in panacinar emphysema is mediated by polys and their proteases is attractive and suggestive evidence supporting this is available. However, more evidence that takes into full account the cell biology of the proteases any poly turnover in the lung are needed to extend the hypothesis and to form a rational basis for therapeutic and prophylactic measures.
目前认为组织蛋白水解酶对全腺泡型肺气肿的发病机制至关重要。多形核白细胞（多形核细胞）在其嗜天青颗粒中有几种酶，包括弹性蛋白酶和组织蛋白酶G。它们在其特异性颗粒中有胶原酶。我们发现这种胶原酶具有双重潜伏性。它具有溶酶体类型的潜伏性，这取决于围绕每个特异性颗粒的单位膜的不渗透性。此外，它还有一种潜伏性，可通过蛋白水解酶转化为活性。一旦胶原酶从其膜依赖性潜伏状态释放出来，嗜天青颗粒中的组织蛋白酶G就是这种潜伏胶原酶的有效激活剂。因此，在分析酶对局部肺部疾病发病机制的贡献时，必须考虑酶的潜伏性、潜伏性的性质以及潜伏酶对激活机制的可及性。同样重要的是，多形核细胞不是正常肺的主要细胞成分。多形核细胞必须被趋化肽吸引到肺部。这些肽必须通过炎症刺激物（如烟颗粒）与补体成分的相互作用释放出来，或者它们必须由其他来源提供。全腺泡型肺气肿中的肺损伤由多形核细胞及其蛋白酶介导的假说很有吸引力，并且有支持这一假说的暗示性证据。然而，需要更多充分考虑蛋白酶的细胞生物学以及肺中多形核细胞更新的证据，以扩展这一假说并为治疗和预防措施形成合理依据。
