Role of phospholipase A(2) in cholesterol gallstone formation is associated with biliary phospholipid species selection at the site of hepatic excretion - Indirect evidence

Phospholipase A(2) plays a role in cholesterol gallstone development by hyd rolyzing bile phospholipids into lysolecithin and free fatty acids. Lysolec ithin and polyunsaturated free fatty acids are known to stimulate the synth esis and/or secretion of gallbladder mucin via a prostanoid pathway, leadin g to enhancing cholesterol crystal nucleation and growth, and therefore, th e action of phospholipase A(2) is associated, in part, with bile phospholip id fatty acid. To clarify this hypothesis, we evaluated the effect on bile lipid metastability in vitro of replacing phospholipids with lysolecithin a nd various free fatty acids. Supersaturated model biles were created with a n identical composition (cholesterol saturation index, 1.8; egg yolk lecith in, 34 mM; taurocholate, 120 mM; cholesterol, 25 mM) except for 5%, 10%, or 20% replacement of egg yolk lecithin with a combination of palmitoyl-lysol ecithin and a free fatty acid (palmitate, stearate, oleate, linoleate, or a rachidonate), followed by time-sequentially monitoring of vesicles and chol esterol crystals using spectrophotometer and video-enhanced differential co ntrast microscopy. Replacement with hydrophilic fatty acids (linoleate and arachidonate) reduced vesicle formation and promoted cholesterol crystalliz ation, whereas an enhanced cholesterol-holding capacity was evident after r eplacement with hydrophobic fatty acids (palmitate and stearate), These res ults indicate that the effect of phospholipase A(2) on bile lithogenecity i s modulated by the fatty acid species in bile phospholipids, and therefore, that the role of phospholipase A(2) in cholesterol gallstone formation is dependent, in part, on biliary phospholipid species selection at the site o f hepatic excretion.