Tissue plasminogen activator production by monocytes in venous thrombolysis

Laminated occlusive thrombus was induced in the rat inferior vena cava (IVC) by a distal stenosis and injection of thrombin. Immunocytochemistry was performed on serial cryostat sections of the thrombus for tissue plasminogen activator (tPA) and a variety of phenotype markers for mononuclear cells. There was little tPA in 2-day-old thrombus. However, tPA was present in significant quantities in 1- and 2-week-old thrombus. Most of the staining for tPA was associated with monocytes, which had infiltrated the thrombus in large numbers. No caval endothelium was seen in these sections. By 4 weeks, the IVC had re-canalized and new endothelium had formed; tPA staining was weakly positive in the endothelium and smooth muscle. In situ hybridization with a digoxigenin-labelled RNA probe confirmed the monocytes as the main source of tPA. This study shows that large numbers of infiltrating monocytes are present in venous thrombosis and that they are the main source of tPA.