我們對很多基質金屬蛋白酶（MMPs）（一個廣泛的鋅依賴型肽鏈內切酶家族）的正常生理作用仍然很不了解,。
現(xiàn)在，基質金屬蛋白酶-12（MMP-12,，亦稱為巨噬細胞彈性蛋白酶）被發(fā)現(xiàn)具有針對革蘭氏陽性和革蘭氏陰性細菌的直接抗菌活性,。MMP-12的這種功能與該分子的羧基端區(qū)域、而不是其催化點有關,。而且令人吃驚的是,，MMP-12在細胞內也具有抗菌活性，因為其MMPs主要是在細胞外空間中具有活性,。這項工作還表明,，巨噬細胞在急性細菌感染最早階段扮演一個角色，人們更為熟悉的是,，這些階段被認為是嗜中性細胞發(fā)揮作用的范疇,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
