Activation of the complement system on the cell surface results in the insertion of pore forming membrane attack complexes (MAC, C5b‐9). In order to protect themselves from the complement attack, the cells express several regulatory molecules, including the terminal complex regulator CD59 that inhibits assembly of the large MACs by inhibiting the insertion of additional C9 molecules into the C5b‐9 complex. Using the whole cell patch clamp method, we were able to measure accumulation of homologous MACs in the membrane of CD59− human B‐cells, which formed non‐selective ion channels with a total conductance of 360 ± 24 pS as measured at the beginning of the steady‐state phase of the inward currents. C5b‐8 and small‐size MAC (MAC containing only a single C9) can also form ion channels. Nevertheless, in CD59+ human B‐cells in spite of small‐size MAC formation, an ion current could not be detected. In addition, restoring CD59 to the membrane of the CD59− cells inhibited the serum‐evoked inward current. The ion channels formed by the small‐size MAC were therefore sealed, indicating that CD59 directly interfered with the pore formation of C5b‐8 as well as that of small‐size C5b‐9. These results offer an explanation as to why CD59‐expressing cells are not leaky in spite of a buildup of homologous C5b‐8 and small‐size MAC. Our experiments also confirmed that ion channel inhibition by CD59 is subject to homologous restriction and that CD59 cannot block the conductivity of MAC when generated by xenogenic (rabbit) serum.

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Tryptophan column immunoabsorption therapy is beneficial to the patient with a neuroimmunological disease, but some complications have been attributed to this treatment. There have been some instances of an abrupt shock state along with severe decreases in blood pressure. In regards to this shock state, it has been reported that plasma bradykinin levels increase during tryptophan column immunoabsorption therapy. In this study, we examined the correlation between plasma bradykinin levels and either blood pressure or the levels of its degrading enzymes, angiotensin converting enzyme (ACE) and carboxypeptidase R (CPR) in 6 patients. Increased concentrations of bradykinin were present in the latter half of the therapeutic interval, and plasma bradykinin levels were found to be inversely correlated to CPR activity. The decreased CPR level could augment the activities of bradykinin. We speculate that bradykinin could be responsible for the hypotension occurring in patients during tryptophan column immunoabsorption therapy and that the metabolism of bradykinin could be caused by the decreased activity of CPR.