ery early in the twentieth century, Paul Ehrlich looked for a "magic bullet," a drug that could affect only invading microorganisms and not host cells, one that could be delivered directly to the area of infection or inflammation. In spite of extensive investigations, Ehrlich did not find a magic bullet, but others carried on the search. Through the years many attempts have been made to attach drugs to various molecules, such as specific antibodies, that could home to the area where the drugs were needed.
Currently, a promising approach to finding the elusive magic bullet is based on ongoing investigations of the mechanisms of inflammation. Early during the inflammatory response, a family of adhesion molecules called selectins is expressed on cells of small blood vessels in the area of injury. Selectins bind to carbohydrate molecules on circulating leukocytes. As the leukocytes roll rapidly through the blood vessels, selectin molecules bind them, stopping them in their tracks. The leukocytes are held captive in the region of inflammation. Other molecules in that area attract the captured white blood cells across the vessel wall and into the injured tissue. Selectin activity is a marker for tissue damage and, therefore, a logical target for delivery of drugs into areas of inflammation resulting from infections. The drugs could be antimicrobials to act against invading microorganisms, or anti-inflammatory agents to lessen the symptoms caused by inflammation.
In some diseases, such as arthritis and other autoimmune diseases, the tissue damage caused by inflammation is the major factor in the disease process. In addition to delivering anti-inflammatory drugs to the area, blocking the actions of selectins by a selectin inhibitor might prevent the development of inflammatory damage.
Scientists working in this area are studying the exact structure of the various selectin molecules and their characteristics. One selectin is stored in cells of the blood vessel and is expressed on the cell surface within minutes of tissue injury. Another is synthesized after injury and expressed on cell surfaces after about 4 hours. The structure of leukocyte surface molecules that will bind to selectins has also been determined. It should be possible to attach antimicrobial or anti-inflammatory drugs to the small portions of binding molecules that actually bind to the selectin. This combination would then be selectively removed from the circulation in the areas of inflammation, the only areas where selectin is produced. It is estimated that preparations of selectin-binding antimicrobials or anti-inflammatory drugs could be available within several years, making Ehrlich's long-ago dream a reality.
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