Lysolecithin

Abstract Lysolecithin (LPC) is the lysophosphatide produced when phospholipase A2 catalyzes the hydrolysis of phosphatidyl choline (lecithin). Phospholipase A2 and LPC are normally found in trace amounts within nerve tissue (15). LPC is a potent natural detergent and has a wide variety of membrane-altering properties, including cytolysis (22). It completely solubilizes brain myelin in vitro and causes demyelination in vivo when injected into the white matter of the CNS or into peripheral nerve (6,10,12). The demyelination is rapid and self-limited, and is quickly followed by remye lination (13,20). These synchronized phases of demyelination and remyelination have made LPC a popular agent for producing experimental models of demyelination and re myelination in the CNS and PNS. There are no recorded cases of toxicity in humans from exogenously derived LPC, but it has been suggested that endogenously derived LPC may have a role in the pathogenesis of a number of disease states (8,22). The absorption, distribution, and excretion of exogenously derived LPC are unknown. The concentration of LPC normally present in nerve tissue is controlled by the phosphatidyl-choline deacylation/lysophosphatidyl-choline reacylation cycle and by lysophosphatidyl-choline deacylation (15). It has been suggested these enzyme systems also neutralize exogenously derived LPC (8,12). Cell membranes are the primary target of LPC; low concentrations of LPC cause a variety of membrane perturbations ranging from altered ionic permeability and activation of membrane bound enzymes, to cytolysis (8,22). The CNS and PNS are the organs principally involved when LPC is administered to laboratory animals (10,12). LPC-induced hemolysis of erythrocytes has been a principal model for in vitro studies (22). Demyelination begins within 30 min after 0.2 µ,l of a 1 % solution of LPC is injected into mouse peripheral nerve in vivo (12). Myelin breakdown starts at Schmidt-Lanterman incisures and adjacent to nodes of Ranvier, and then spreads to involve the entire internode (9,12).