Breakdown of articular cartilage proteoglycans by lymphokine-activated macrophages

Lymphokine supernatants (L_E) prepared from antigen sensitive lymphocytes caused an inhibition of migration of macrophages from capillary tubes. Control supernatants (L_C) had no effect. The lymphokine supernatants, when added to macrophage cultures (the equivalent of 60 × 10⁶ lymphocytes added to 40×l0⁶ 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 L_C was added. The macrophage supernatants (L_E but not L_C) 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.