MEMBRANE-PROTEINS THAT PROTECT AGAINST COMPLEMENT LYSIS

Human cells express a battery of complement regulatory molecules which allow them to survive the continuous low-level complement attack which occurs on all cells exposed to plasma or other biological fluids. An explosion in our knowledge of the structures and mechanisms of action of these regulators has occurred in the last few years as a result of the molecular cloning of all but one (HRF) of the five known inhibitors. The three inhibitors of the C3/C5 convertases are functionally and structurally similar and have arisen from a common ancestor gene. The MAC inhibitors also appear to be functionally similar to each other but structural comparison awaits the cloning of HRF. The relative importance of these inhibitors is likely to vary between tissues, but in the few instances where this has been studied in detail, CD59 and DAF appear to be the most important in allowing cells to survive complement attack [9,131]. For effective protection it is likely that control is required both at the level of the C3/C5 convertase and at the level of the MAC. Many of the regulatory molecules may subserve other functions which may be equally or more important than their role in control of complement. The potential clinical applications of these regulatory molecules are just beginning to be realized and will undoubtedly be a major focus of research over the next few years. © 1994 Springer-Verlag.