Breakdown of articular cartilage proteoglycans by lymphokine-activated macrophages.

Lymphokine supernatants (LE) prepared from antigen sensitive lymphocytes caused an inhibition of migration of macrophages from capillary tubes. Control supernatants (LC) had no effect. The lymphokine supernatants, when added to macrophage cultures (the equivalent of 60 x 10(6) lymphocytes added to 40 x 10(6) macrophages), activated the macrophages so that they secreted the enzyme collagenase after 48 h and 72 h of culture. No collagenase was detected before 48 h or from macrophage supernatants to which LC was added. The macrophage supernatants (LE but not LC) also contained factors (probably enzymes) that, when added to a piece of articular cartilage in medium, caused a partial loss of the hexosamine content of the articular cartilage. These changes were seen as early as after 24 h of culture. Activated macrophages therefore release enzymes that can completely destroy cartilage. Both collagenase and a proteoglycan-hydrolyzing enzyme are released which in vivo might be responsible for the cartilage damage that is found in diseases such as rheumatoid arthritis.