MONOCYTE PROCOAGULANT ACTIVITY-INDUCED BY IN-VIVO ADMINISTRATION OF THE OKT3 MONOCLONAL-ANTIBODY

The first injection of OKT3 in kidney transplant recipients activates the common pathway of coagulation. This may result in early thrombosis of graft vessels. To this day, the cells involved in this phenomenon have not been identified, The aim of this study was to investigate whe ther circulating monocytes participated in this OKT3-induced coagulopa thy. The procoagulant activity (PCA) of circulating monocytes rose fro m (mean +/- SEM) 0.15 +/- 0.02 mU/mL to 0.40 +/- 0.05 mU/mL at 3 hours (P = .002) and 0.56 +/- 0.21 at 5 hours (P = .045) after the initial OKT3 injection. These monocytes displayed increased tissue factor expr ession at the same moments (mean fluorescence intensity: 14 +/- 2 befo re OKT3 injection versus 54 +/- 14 at 3 hours, P = .008 and 34 +/- 7 a t 5 hours, P = .01). Tissue factor mRNA was detected in blood by rever se transcriptase-polymerase chain reaction as early as 2 hours after O KT3 administration. The circulating monocytes also displayed a steady increase in membrane expression upregulation of ICAM-1, CD29, CD11b, a nd CD11c. In vitro experiments showed that OKT3 as well as 2 mitogenic , humanized anti-CD3 antibodies potently induced monocytic PCA whereas the 4 nonmitogenic anti-CD3 antibodies tested were over 1,000-fold le ss potent than OKT3. We conclude that (1) OKT3 induces in vivo tissue factor gene upregulation and membrane expression resulting in increase d PCA of circulating monocytes; and (2) nonmitogenic anti-CD3 antibodi es seem devoid of significant procoagulant properties. (C) 1996 by The American Society of Hematology.