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 whether circulating monocytes participated in this OKT3-induced coagulopathy. The procoagulant activity (PCA) of circulating monocytes rose from (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 expression at the same moments (mean flourescence intensity: 14 +/- 2 before OKT3 injection versus 54 +/- 14 at 3 hours, P = .008 and 34 +/- 7 at 5 hours, P = .01). Tissue factor mRNA was detected in blood by reverse transcriptase-polymerase chain reaction as early as 2 hours after OKT3 administration. The circulating monocytes also displayed a steady increase in membrane expression upregulation of ICAM-1, CD29, CD11b, and 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 less potent than OKT3. We conclude that (1) OKT3 induces in vivo tissue factor gene upregulation and membrane expression resulting in increased PCA of circulating monocytes; and (2) nonmitogenic anti-CD3 antibodies seem devoid of significant procoagulant properties.
Pradier
O
O
Department of Hematology-Immunology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Surquin
M
M
Stordeur
P
P
De Pauw
L
L
Kinnaert
P
P
Vereerstraeten
P
P
Capel
P
P
Goldman
M
M
Abramowicz
D
D
D001777:Blood Coagulation / Q000187:drug effects*; D002478:Cells, Cultured; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D016030:Kidney Transplantation; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D016853:Muromonab-CD3 / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology
D016853:Muromonab-CD3