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Scientists at the Consejo Superior de Investigaciones Científicas (CSIC), University of Pittsburgh and Brigham and Women's Hospital Boston (USA) have identified a new defense mechanism of cells in the lung against bacterial infections, such as emphysema or pneumonia. The investigation, which is published in the latest issue of the journal Nature, helps to understand the mechanisms of human body's defense against bacterial attacks, and could lead to new antimicrobial therapies.

The study, in which the researcher has participated CSIC, F. Xavier Gomis-Ruth, Institute of Molecular Biology of Barcelona (CSIC), located in the Barcelona Science Park, focuses on the enzyme matrix metalloproteinase 12 (MMP-12). This enzyme, expressed by macrophages (a type of white blood cell) lung, has antimicrobial activity. In fact, it is known to be implicated in diseases such as emphysema, but no data were available about the role they played. In this work, which has contributed to the investigation of the CSIC, is described how it works and it has been determined the region of the protein responsible.

Discover a defense mechanism of lung cells against bacterial infections The researchers started from the hypothesis that MMP-12 was involved in the defense against bacteria. To confirm this, the team conducted a trial with two groups of rodents, one normal and one genetically modified to not produce the enzyme MMP-12. After subjecting both groups to a bacterial infection by S. aureus and E. coli, two bacterial models widely used in scientific studies, the authors concluded that the group of rodents without MMP-12 showed a 50% increased mortality from infection in the lungs and peritoneum. In later trials, the rodents without MMP-12 also showed higher mortality in the case of pneumonia.

Macrophages play a key role in the immune defense through the ingestion of infectious microorganisms and removing dying cells and cells that have died by programmed cell death. The scientific community has also found that macrophages kill bacteria by lysozyme or molecules such as nitric oxide. In this study, the researchers reveal an alternative mechanism used by these cells in the human defense system to cope and overcome bacterial infections.

Specifically, the research team that has participated in Gomis has been observed by transmission electron microscopy and scanning electron microscopy that the enzyme MMP-12 acts by breaking the outer membrane of bacteria. As the researcher explained the CSIC, "once the macrophage phagocyte pathogenic bacterial cells, they are locked in some intracellular compartments known as fagolisosomas. Is when items of MMP-12 are transferred to these compartments, where they attach to bacterial cell wall causing its disruption and subsequent cell death. "

The investigations described have determined that the anti-loop lies in a very specific C-terminal domain, known as type hemopexina of MMP-12. Since synthetic peptides generated from the rodent MMP-12, containing the sequence-aminoacide found a chain of 20 amino acids that have designated SR-20, researchers have managed to reproduce the antimicrobial activity.