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“…Resistance mechanisms might operate either by increasing the rate of removal of ions sufficiently to overcome the MAC-induced influx, or by removing or inactivating the membrane-bound MAC thereby preventing further influx. Inhibition ofion pumps has been shown to have little effect on nucleated cell resistance to lysis, suggesting that, at least in the cell line used, the first strategy outlined above is not of major importance (Ramm et al, 1984). There is now however abundant evidence for the second strategy, and this will be reviewed in the next section.…”
Section: Introductionmentioning
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“…Resistance mechanisms might operate either by increasing the rate of removal of ions sufficiently to overcome the MAC-induced influx, or by removing or inactivating the membrane-bound MAC thereby preventing further influx. Inhibition ofion pumps has been shown to have little effect on nucleated cell resistance to lysis, suggesting that, at least in the cell line used, the first strategy outlined above is not of major importance (Ramm et al, 1984). There is now however abundant evidence for the second strategy, and this will be reviewed in the next section.…”
Section: Introductionmentioning
“…This structure would appear to support Mayer's hyothesis, albeit with a different molecular composition of the ring itself. However, several lines of evidence suggest that this rigid lesion is not necessary for the expression of MAC effects: C9 which has been proteolytically modified to prevent ring polymer formation is fully lytically active (Dankert & Esser, 1985;Morgan et al, 1987b); MACs containing only a single C9 molecule per complex cause efficient lysis of erythrocytes (Bhakdi & Tranum-Jensen, 1986); functional studies indicate that only four C9 molecules per C5b-8 complex are required to form a lesion through which large molecules can pass (Ramm et al, 1984); and immunochemical studies show that an average of only three or four C9 molecules are bound per C5b-8 complex on complement-lysed cells (Sims, 1983;Stewart et al, 1984).…”
Section: Introductionmentioning
“…The first hypothesis can be tested by adding growth fac- The latter hypothesis can be tested by treating the target cells with puromycin. Puromycin inhibits protein synthesis and it has been shown to increase the osmotic fragility of nucleated cells; to reduce the rate of ion pumping; to reduce the rate of membrane repair by affecting the synthetic capability of the cell; and to reduce the rate of channel elimination (Ramm, Whitlow and Mayer, 1984). All these factors combine to make the cells more susceptible to lysis.…”
Section: Cloningmentioning