Fibrin Deposition and Clearance in Chronic Granulomatous Inflammation: Correlation with T-Cell Function and Proteinase Inhibitor Activity in Tissue

Abstract

Patterns of fibrin deposition were investigated by immunofluorescence microscopy in livers of thymus intact (TI) and athymic (AT) mice infected with Schistosoma mansoni. Thrombin and fibrinolysis inhibitor activity in tissue extracts also were measured. In TI mice fibrin was detected perivascularly by 6 weeks after infection and at 8 weeks it was found over the granulomas as they developed. Fibrin was cleared from the center of granulomas by 10 weeks. Thrombin inhibitor activity increased at 4 to 6 weeks but declined below control levels later as granulomas formed. Fibronolysis inhibitor activity, on the other hand, peaked at 9 to 12 weeks after infection. In AT mice extensive fibrin deposition was detected in the liver throughout the period when smaller and incomplete granulomas developed. Central clearing did not occur. Thrombin inhibitor activity greatly increased by 8 weeks after infection but fibrinolysis inhibitor activity remained unchanged. These findings suggest that fibrin deposition and firbinolysis are orderly events regulated in the lesions by proteinases and their inhibitors and this seems to be a general tissue reaction in the early stage of chronic granuloma formation. Since local clearance of fibrin in vivo and fibrinolysis inhibitor activity from tissue extracts studied in vitro are more evident in TI mice than in AT mice, it appears that T cell fu;ction is important in modulating the tissue response during granulomatous inflammation.