Mammalian blood coagulation is triggered when factor VIIa binds productively to tissue factor (TF). TF resides on the cell surface in a cryptic configuration that can rapidly transform into an active configuration upon disruption of the cell. We have suggested that the disulfide bond in the membrane proximal domain (Cys186-Cys209) of TF is involved in de-encryption. 1 This bond has an–RHStaple configuration, which is a feature of allosteric disulfides. 2

Several observations support a mechanism where the bond is broken in the cryptic form of the protein and activation involves formation of the disulfide. 1, 3-5 For example, the thiol-alkylating agent, methyl methanethiolsulfonate (MMTS), blocks TF activation and the thiol-oxidising agent, HgCl2, promotes activation. This proposal was recently questioned by Pendurthie et al. 6 These investigators used the human breast carcinoma cell line MDA-MB231 to study TF de-encryption. In this letter we compare and contrast TF de-encryption in MDA-MB231 cells with 3 other human monocytic cell types. Myeloid leukemia HL60 cells7 and monocytic U937 cells8 were differentiated with phorbol myristate acetate (PMA), which also triggers TF expression. 9 PMA treatment did not change TF expression in monocytic THP1 cells.