New endogenous CXC chemokine ligands as potential targets in lung emphysema

Chronic respiratory inflammation is caused by a sustained influx of macrophages and neutrophils, which leads to tissue remodeling and collagen breakdown. Recently, we have identified collagen-breakdown products that can activate and attract inflammatory cells via the CXC (two cysteines with an inverting amino acid)1 and CXC2 receptors (CXCR1 and CXCR2). By using a technique called 'inverted hydropathy', small peptides were synthesized that interact specifically with the responsible collagen-breakdown products and inactivate them. After inactivation, the collagen-breakdown products are no longer able to bind to their receptors. These neutralizing peptides inhibited neutrophil influx, heart hypertrophy and lung emphysema in animal models, and they are likely to be useful in other diseases that are characterized by a chronic inflammation, such as rheumatoid arthritis and inflammatory bowel diseases, where neutrophils are potential target cells. In this opinion article we will present a new hypothesis through which the chronicity and remodeling of tissue of several inflammatory diseases could be explained.