Perforin: structure, function, and regulation.

Abstract

The mechanism of lymphocyte-mediated cytolysis is controversial (see recent reviews Bleackley et al. 1988; Brunet et al. 1988; Clark et al. 1988; Mueller et al. 1988; Müller-Eberhard 1988; Munger et al. 1988; Nagler-Anderson et al. 1988; Sitkovsky 1988; Young et al. 1988; Podack et al. 1988; Jenne and Tschopp 1988a, b; Bleackley 1988; Hershberger et al. 1988; Stevens et al. 1988; Tschopp and Nabholz 1990; Podack et al. 1991). The main contentions concern the question whether secretory functions of the killer cell, as proposed by the vectorial granule secretion model of cytotoxicity (Podack 1985; Henkart 1985), are required for target cell lysis and whether secretory models of cytotoxicity account for most of the cytotoxic activity. Other open questions are related to the role of DNA degradation (apoptosis, programmed cell death) in target cell lysis (Russel et al. 1982; Russel 1983; Duke et al. 1983; Lovell and Martz 1987) and how this process is mediated molecularly. No molecular tools are available at the present time to assess the importance, or even existence, of the putative secretion-independent pathway of lymphocyte-mediated cytolysis. Similarly, since the mechanism of DNA degradation is not understood, it is difficult to quantitate its role in cytolysis.