Impaired cytoprotective function of muscle in human gallbladders with cholesterol stones

Abstract

Acute cholecystitis develops in gallbladders (GB) with excessive bile cholesterol (Ch). Increased membrane Ch content affects membrane function and may affect PGE2receptors involved in the cytoprotection against acute inflammation. This study was aimed at determining whether the cytoprotective response to PGE2is affected by lithogenic bile with Ch. Muscle cells from human GB with cholesterol stones (ChS) or pigment stones (PS) were obtained by enzymatic digestion. PGE2levels were measured by radioimmunoassay, and activities of superoxide dismutase (SOD) and catalase were assayed by spectrophotometry. The contraction in response to H2O2in muscle cells from PS was 14 ± 0.3%, not different from normal controls, and decreased after the cells were incubated with Ch-rich liposomes ( P < 0.05), which increase the Ch content in the plasma membranes. In muscle cells from GB with ChS, H2O2-induced contraction was only 9.2 ± 1.3% and increased to 14 ± 0.2% after Ch-free liposome treatment to remove Ch from the plasma membranes ( P < 0.01). H2O2caused a similar increase in the levels of lipid peroxidation and PGE2content in muscle cells from GBs with ChS and PS. However, the activities of SOD and catalase were significantly lower in muscle cells from GBs with ChS compared with those with PS. The binding capacity of PGE2receptors was also significantly lower in muscle cells from GBs with ChS compared with those with PS. In conclusion, the cytoprotective response to reactive oxygen species is reduced in muscle cells from GBs with ChS despite a normal increase in the cellular levels of PGE2. This impaired cytoprotective response may be due to a dysfunction of PGE2receptors with decreased binding capacity resulting from excessive Ch levels in the plasma membrane.