Tissue damage typically stimulates an influx of leukocytes, white blood cells known for promoting tissue regeneration and healing--to tissue protecting organs. However leukocytes can be a double edged sword. In the May 2006 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), researchers at Baylor College of Medicine and the Michael E DeBakey Veterans Affairs Medical Center in Houston, Texas, present the results of a study to test the hypothesis that leukocytes extend the zone of damage and cell death in cartilage after an acute injury.
The research team began with a collection of dog bones--the hind knee joints of 24 fresh young adult cadaver canines. Within one hour after death, each bone was subjected to impact injury with a metal weight, determined sufficient to cause cartilage damage without shattering the bone. A comparable collection of cadaver canine bones was preserved to serve as controls. All of the knee joints were cultured with blood leukocytes from the same dogCartilage biopsies were taken at various intervals between 12 hours and 7 days.
Among the assaulted bones, approximately half of the chondrocytes, or cartilage cells, died within 7 days. In the uninjured bones, over 90 percent of the chondrocytes survived. A surprising finding was the reduced viability of cartilage cells located well outside the vicinity of direct impact. In cartilage samples taken 6 to 9 mm from the impact site, and even in samples taken 10 mm or more from the impact site, these critical cells to tissue renewal had largely been killed off by leukocytes. The real culprit, however, was the leukocytes' generation of noxious nitric oxide (NO).
Is there a way to stop the leukocyte-mediated murders of chondrocytes? To explore this critical question, the researchers conducted more experiments on the dog bone cultures. They found that the killing of cartilage cells could be averted by desferoxamine, chemical thay=t blocks production of NO, and by anti-CD18 antibodies, which block the Velcro-like adhesion molecules that white cells use to adhere to other cells.
"Our findings have interesting clinical implications," observes the study's leading author, Dr. D. M. Green. "First, we have demonstrated that acute mechanical injury of the articular surface causes death of chondrocytes located at a distance from the site of trauma. Second, up-regulation of adhesion molecules on the affected chondrocytes allows leukocytes to adhere and to extend the zone of injury beyond the impact site. Thus, the data in this study suggest that therapies to reduce acute influx of leukocytes into damaged cartilage should be considered in the future when treating osteochondral injuries."
Article: "Cellular Events Leading to Chondrocyte Death After Cartilage Impact Injury," D.M. Green, P.C. Noble, J.S. Ahuero, and H.H. Birdsall, Arthritis & Rheumatism, May 2006, 54:5, pp. 1509-1517.
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