Inflammation is usually a normal and beneficial response by the body to tissue injury or infection. But sometimes it can spiral out of control and lead to serious complications and diseases including pulmonary fibrosis, asthma and inflammatory bowel disease. Researchers have uncovered a mechanism that regulates the inflammatory response during tissue repair, providing the first specific molecular targets for developing ways to prevent highly destructive and potentially fatal inflammatory reactions.From the Washington University School of Medicine :Protein Regulates Inflammatory Response
St. Louis, Nov. 26, 2002 ? Inflammation ? a normal and beneficial response to tissue injury or infection ? can sometimes spiral out of control and lead to serious complications and diseases including pulmonary fibrosis, asthma and inflammatory bowel disease.
Researchers at Washington University School of Medicine in St. Louis have uncovered a mechanism that regulates the inflammatory response during tissue repair, providing the first specific molecular targets for developing ways to prevent highly destructive and potentially fatal inflammatory reactions.
The study, led by William C. Parks, Ph.D., professor of pediatrics, medicine and cell biology and physiology, was published in the Nov. 27 issue of the journal Cell.
The inflammatory process often is initiated in epithelial tissues, which form a protective barrier that lines the surfaces and cavities of the body and are the first line of defense against invading microorganisms.
One characteristic of inflammation is the accumulation of white blood cells, called neutrophils, which destroy bacteria. Neutrophils do not become active until they reach the site of tissue damage, probably because this is where they are most likely to encounter pathogens. While neutrophils are certainly very good at destroying invading microorganisms, they also can damage or destroy normal tissue.
Park’s team found that when lung epithelia were damaged in mice, two proteins called matrilysin and KC were made. KC then formed a complex with a protein called syndecan-1 that was attached to the surface of the epithelial cells. Matrilysin then caused the syndecan-1/KC complex to be released from the cell surface, where it accumulated at the damage site and attracted neutrophils.
The scientists also demonstrated that matrilysin is critical for progression of the inflammatory response. In fact, mice lacking this protein survived an otherwise lung-damaging treatment because they had a greatly reduced inflammatory response.
According to Parks, these results provide a new mechanism to explain a critical step of the inflammatory reaction not previously understood.
“A shortcoming with many anti-inflammatory therapies is the lack of specific drugs that target defined steps in the early, critical period of inflammation,” Parks says. “Not only do our results show how the epithelium guides neutrophils to sites of injury, they also suggest that blocking matrilysin or syndecan-1 would provide a therapeutic strategy for preventing acute inflammation.”