Enzyme used for AIDS treatments may be tapped to fight Arthritis

• The finding by researchers at Washington University School of Medicine in St. Louis shows that an enzyme known as cathepsin G regulates the ability of immune cells known as neutrophils to secrete chemicals that attract other immune cells and start the local inflammatory process.
• "Cathepsin G affects a very early step in this kind of immune response, so inhibiting it has attractive potential for developers of therapeutics," says senior author Christine T.N. Pham, M.D., assistant professor of medicine and a rheumatologist at Barnes-Jewish Hospital.
• One principal type of treatment for HIV, the virus that causes AIDS, inhibits proteases, so scientists who try to block cathepsin G's role in inflammation will already have an extensive body of research results to refer to.
• Pham's lab uses mouse models of arthritis to study the contributions of proteases and other factors to inflammation and arthritis.
• One such model involves injecting mice with collagen from calf joints.
• "The mice make antibodies to that protein because it's somewhat foreign, but the antibodies have enough cross-reactivity that they will bind to the mouse's own cartilage and collagen and initiate an inflammation," Pham explains.
• "This leads to a condition similar to rheumatoid arthritis in the mice."
• Three years ago, Pham's lab published results showing that mice deficient in cathepsin G and other closely related proteases failed to develop arthritis after the injections.
• Observations made by Pham's lab and other groups had linked the earliest stages of inflammation in the animal models to neutrophils, which are a kind of immune system firestarter.
• They arrive first at sites of injury, infection or irritation and secrete chemicals that bring in secondary waves of other immune attack cells.
• "The way these integrins rearrange and cluster on the cell surface can send a signal back into the cell that modifies the cell's behavior, allowing it to do things like secrete inflammatory factors," Pham explains.