Untersuchungen über die Abhängigkeit der cytolytischen Wirkung des Lysolecithins von Membranenzymen

Abstract

The cytolytic activity of lysolecithin (LL) has been found to be dependent on lysophosphatidespecific enzymes in the cell membrane. The present report deals especially with the analyses of an acyltransferase (LL → lecithin) and of a phospholipase B (LL → glyceryl-phosphoryl-choline) in various cells. It was found that changes in the enzyme activities — as mediated by changes of temperature, of pH, by enzyme inhibitors, or by sensitization of cells with antibody and components of complement — at the same time cause changes of the cytolytic activity of LL. The enhanced LL-cytolysis at reduced temperatures, as well as after addition of p-chloro-mercuri-benzoate (PMB), can accordingly be explained by the inhibition of lysophosphatide-specific enzyme (s) in a way that LL will consequently be of enhanced and/or prolonged action. The PMB-inhibited enzymes can be reactivated by cysteine and concomitantly the extent of LL-cytolysis is reduced. With the aid of C14-lysolecithin it was demonstrated that the concentration of ATP and coenzyme A in the cell is of prime influence in the dynamics of LL, which either will be transformed into membrane-fixed lecithin — and thus additionally stabilizing the cell — or will be degraded to glyceryl-phosphoryl-choline. This regulating mechanism would explain the different sensitivity of fresh and aged cells towards LL-lysis. The described experiments were done with erythrocytes. Preliminary experiments suggest that the same mechanism occurs also in nucleated cells and in bacteria. In view of the lysolecithin theory of complement-mediated cytolysis (FISCHER and HAUPT) the relative activity of lysophosphatide-specific enzymes in cell membranes offers a possible explanation for the different sensitivity of many types of cells towards lysis by complement. On the basis of these results, the significance of lysophosphatides as regulators of hemo- and cytodynamics, as postulated in the thirties by BERGENHEM and FAHRAEUS, is again underlined.