GALLBLADDER MUCOSAL PROTEIN SECRETION DURING DEVELOPMENT OF EXPERIMENTAL CHOLECYSTITIS

The development of experimental cholecystitis produced by lysophosphat idylcholine is associated with reversal of the normal absorptive chara cteristics of gallbladder mucosa, resulting in the intraluminal accumu lation of water, glycoprotein, and protein. The purpose of the present study was to attempt to ascertain if the protein leaks into the lumen because of the cytolytic properties of lysophosphatidylcholine or if it is due to an active secretory process and to characterize the prote in produced. Experiments were performed on anesthetized cats undergoin g gallbladder perfusion with and without lysophosphatidylcholine. The amount of protein in the perfusate was measured and albumin clearance from blood to gallbladder lumen was calculated with and without the ad ministration of vesicular transport inhibitors. In separate experiment s, control and lysophosphatidylcholine (LPC) produced gallbladder perf usates were collected and the protein subjected to SDS-PAGE to ascerta in the nature of the protein secreted. Inhibitors of both microtubular and microfilament activity decreased the protein accumulation and cle arance produced by lysophosphatidylcholine. Gallbladder white blood ce ll accumulation and inflammation as evaluated by P-glucuronidase and p rostaglandin E levels were not significantly altered by cytochalasin o r colchicine administration. Lysphosphatidylcholine also produced sign ificant increases in perfusate LDH levels. The protein produced was pr imarily a 66-kDa protein. Transfer of the protein to a nitrocellulose membrane and immunoblotting with anti-albumin antibody demonstrated th at the protein was albumin. The results Suggest that during the develo pment of cholecystitis, lysophosphatidylcholine produces albumin accum ulation in the gallbladder primarily by inducing an active secretory p rocess resulting in gallbladder distension.