INCREASED BILIARY GROUP-II PHOSPHOLIPASE A(2) AND ALTERED GALLBLADDERBILE IN PATIENTS WITH MULTIPLE CHOLESTEROL STONES

Background & Aims: Multiple cholesterol stones are associated with mor e biliary complications and show more rapid cholesterol nucleation tha n solitary stones, Group II phospholipase A(2) (PLA(2)-II) may play a critical role in the process of mucosal inflammation, which in turn ma y produce pronucleating agents. PLA(2)-II concentrations in gallbladde rs and gallbladder bile from patients with different types of gallston e disease were assayed to correlate PLA(2)-II with alterations in bili ary composition, Methods: PLA(2)-II protein concentrations were assaye d immunoradiometrically using monoclonal antibodies against human sple nic PLA(2)-II. Results: Immunoreactive PLA(2)-II levels in gallbladder bile were significantly higher in patients with multiple cholesterol stones (68.2 +/- 6.3 ng/dL, mean +/- SEM; n = 24) than in those with s olitary stones (24.9 +/- 2.8; n = 20; P < 0.01), those with multiple p igment stones (24.2 +/- 3.7; n = 18; P < 0.01), or control subjects (1 3.4 +/- 1.7; n = 19; P < 0.01), increased biliary immunoreactive PLA(2 )-II levels in multiple cholesterol stones were associated with a conc omitant increase in the lysophosphatidylcholine to phosphatidylcholine ratio; free arachidonate, protein, and hexosamine concentrations; and gallbladder bile viscosity, The gallbladders showed an increased PLA( 2)-II protein mass and steady-state messenger RNA levels, which was as sociated with increased prostaglandin E-2 levels, Conclusions: Increas ed biliary PLA,II may be of pathogenetic importance in multiple choles terol stones, probably through potentiating gallbladder mucosal inflam mation with associated biliary alterations favoring cholesterol crysta l formation.