The Chemotaxis of Selected Cell Types to Connective Tissue Degradation Products

Because rheumatoid inflammation is associated with the presence of large numbers of leukocytes in joint effusions, the question of whether enzymatic splitting of collagen and fibrin can lead to generation of chemotactic factors was investigated. Fibrinogen was purified from the plasma of four different species, and the homogeneity of the preparations was established by physicochemical and immunologic techniques. Fibrin was prepared and then lysed with plasmin to obtain fibrin degradation products (FDP). Similarly, purified collagenase was used to lyse collagen in vitro, and the chemotactic activity of the reaction mixtures was analyzed. The experiments presented indicate that fibrinogen, fibrin, and plasmin do not possess any intrinsic chemotactic activity. However, when fibrin was split by plasmin, FDP of human, bovine, sheep, and equine origin all proved to be strong leukotactic agents for polymorphonuclear leukocytes (PMN). Purified collagenase per se was found to be a cell type-specific chemotactic agent for PMN. Not only were collagen degradation products not chemotactic, but they also inhibited the leukotactic activity of the purified collagenase. Furthermore, this inhibition of the chemotactic activity of collagenase was independent of its enzymatic activity. The results presented suggest that there is a direct correlation between the process of fibrinolysis and the chemotactic attraction of leukocytes and between the presence of collagenase and leukotaxis. This system may serve as a model to explain the mechanisms by which cells accumulate in inflamed joints.