Role of thrombin and plasmin in development of delayed hypersensitivity reaction in guinea pig skin.

Induration is a prominent feature of delayed hypersensitivity reaction (DHR), and fibrin deposition is the central mechanism. We studied the effects of two inhibitors of DHR on the activities of thrombin and plasmin in the extract of the skin site of DHR and compared the two activities in the site of DHR with those in the site of the Arthus reaction (AR) that lacks induration. Warfarin, an anticoagulant, inhibited thrombin activity and induration, but not plasmin activity. Ferritin, a blocker of a macrophage-dependent reaction, inhibited the two activities and induration. The lesion of DHR had three to four times the thrombin activity of the lesion of AR, and the activity paralleled the development of induration. In contrast, plasmin activity of the site of DHR was lower than that of the site of AR and was associated with the reduction of induration. The two protease activities in the site of AR did not correlate with the development of the AR lesion. These results suggest that thrombin and plasmin mediate the development of induration and that induration is produced by a synergistic effect of high thrombin activity and low plasmin activity in the site of DHR.