我们对很多基质金属蛋白酶（MMPs）（一个广泛的锌依赖型肽链内切酶家族）的正常生理作用仍然很不了解。
现在，基质金属蛋白酶-12（MMP-12，亦称为巨噬细胞弹性蛋白酶）被发现具有针对革兰氏阳性和革兰氏阴性细菌的直接抗菌活性。MMP-12的这种功能与该分子的羧基端区域、而不是其催化点有关。而且令人吃惊的是，MMP-12在细胞内也具有抗菌活性，因为其MMPs主要是在细胞外空间中具有活性。这项工作还表明，巨噬细胞在急性细菌感染最早阶段扮演一个角色，人们更为熟悉的是，这些阶段被认为是嗜中性细胞发挥作用的范畴。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 460, 637-641 (30 July 2009) | doi:10.1038/nature08181
Macrophage elastase kills bacteria within murine macrophages
A. McGarry Houghton1,4, William O. Hartzell2,4, Clinton S. Robbins1, F. Xavier Gomis-Rüth3 & Steven D. Shapiro1
1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
2 Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
3 Proteolysis Lab, Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park, Helix Building, c/ Baldiri Reixac 15-21, 08028 Barcelona, Spain
4 These authors contributed equally to this work.
Macrophages are aptly positioned to function as the primary line of defence against invading pathogens in many organs, including the lung and peritoneum. Their ability to phagocytose and clear microorganisms has been well documented1, 2. Macrophages possess several substances with which they can kill bacteria, including reactive oxygen species, nitric oxide, and antimicrobial proteins3, 4, 5, 6, 7, 8, 9. We proposed that macrophage-derived proteinases may contribute to the antimicrobial properties of macrophages. Macrophage elastase (also known as matrix metalloproteinase 12 or MMP12) is an enzyme predominantly expressed in mature tissue macrophages10 and is implicated in several disease processes, including emphysema11. Physiological functions for MMP12 have not been described. Here we show that Mmp12-/- mice exhibit impaired bacterial clearance and increased mortality when challenged with both Gram-negative and Gram-positive bacteria at macrophage-rich portals of entry, such as the peritoneum and lung. Intracellular stores of MMP12 are mobilized to macrophage phagolysosomes after the ingestion of bacterial pathogens. Once inside phagolysosomes, MMP12 adheres to bacterial cell walls where it disrupts cellular membranes resulting in bacterial death. The antimicrobial properties of MMP12 do not reside within its catalytic domain, but rather within the carboxy-terminal domain. This domain contains a unique four amino acid sequence on an exposed loop of the protein that is required for the observed antimicrobial activity. The present study represents, to our knowledge, the first report of direct antimicrobial activity by a matrix metallopeptidase, and describes a new antimicrobial peptide that is sequentially and structurally unique in nature.
