Cytolytic mechanism

Smyth, M.J. Norisha, Y. and Ortaldo, J.R (1992). Multiple cytolytic mechanisms displayed by activated human peripheral blood T cell subsets. J. Immunol. 148, 55-62. 

The characteristics and possible mechanisms of action of cytolytic peptides isolated from sea anemones during the past 20 years are described. These agents fall into three categories (1)... 

Modeling Pardaxin Channel. The remarkable switching of conformation in the presence of detergents or phospholipid vesicles (5) suggests that pardaxin is a very flexible molecule. This property helps to explain the apparent ability of pardaxin to insert into phospholipid bilayers. In addition, it is consistent with the suggestion that the deoxycholate-like aminoglycosteroids (5,7) present in the natural secretion from which pardaxin is purified (5) serve to stabilize its dissociated conformation. The question of the mechanism by which pardaxin assembles within membranes is important for understanding pore formation and its cytolytic activity (5). 

The latter behavior is significant because the P. brevis would be rendered ineffective and ichthyotoxins would presumably not be released from sessile cells. All fractions (Fig. 1) were investigated by Pabon and Martin (25). After initial screening of fractions (Figure 1) for activity, it appeared that sessile-formation activity was associated with first ten fractions (minus cytolytic fraction 7), and further investigation indicated that fraction 4 was responsible for induction of cytolysis (at 500 ppb). Clearly, additional studies are in order, but the evidence of a mechanism that causes an additional disfunction of P. brevis cells is encouraging. 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could... 

Acute cellular rejection involves infiltration of macrophages and lymphocytes into the graft and is evident from the necrosis of the parenchymal cells of the graft. The lysis of the parenchymal cells of the transplanted tissue is achieved by the infiltrating leukocytes. Acute cellular rejection may be the product of several mechanisms including cytolytic T-cell-mediated lysis, NK cell-mediated lysis and activated macrophage-mediated lysis. The acute cellular rejection predominantly involves CD8+ T cytolytic cells that kill the grafted tissue. 

Hydi oxydopaniine a neurohansmitter analogue that depletes noradrenergic stores in nerve endings and reduces dopamine levels in brain. Its mechanism of action is linked to cytolytic free-radical production. 

Conolysin-Mt is a linear amphoteric conopeptide with cytolytic properties. The mechanism whereby this peptide disrupts cellular membranes has been compared to that of melittin, a well-characterized component of bee venom. However, conolysin-Mt is capable of selectively disrupting eukaryotic membranes as opposed to bacterial ones. 

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