No abstract

Operative cholangiography has a protective effect for complications of cholecystectomy. Compared with OC, LC carries a nearly twofold higher risk of major bile, vascular, and bowel complications. Further study is required to determine the extent to which potentially preventable factors contribute to this risk.

IgA is thought to neutralize viruses at the epithelial surface of mucous membranes by preventing their attachment. Since IgA, a polymeric immunoglobulin, is transported through the lining of epithelial cells by the polymeric-immunoglobulin receptor and since viruses are obligate intracellular parasites, we hypothesized that IgA antibodies may also interfere with viral replication by binding to newly synthesized viral proteins within infected cells. Polarized monolayers of Madin-Darby canine kidney epithelial cells expressing the polymeric-immunoglobulin receptor were infected on the apical surface with Sendai virus. Anti-Sendai virus IgA monoclonal antibody delivered from the basolateral surface colocalized with viral protein within the cell, as documented by immunofluorescence. More importantly, anti-viral IgA reduced virus titers greater than 1000-fold (P less than 0.0001) in apical supernatants and greater than 10-fold (P less than 0.0001) in cell lysates from monolayers treated with anti-viral IgA compared with those treated with either anti-viral IgG or an irrelevant IgA monoclonal antibody. We believe that the differences in viral titers between cell layers treated with specific IgA, which enters the epithelial cell by binding to the polymeric-immunoglobulin receptor, and those treated with specific IgG, which does not enter the cells, or irrelevant IgA indicate that specific intracellular IgA antibodies can inhibit viral replication. Thus, in addition to the classical role of humoral antibodies in extracellular defense, IgA antibody may be able to neutralize microbial pathogens intracellularly, giving IgA a role in host defense that has traditionally been reserved for cell-mediated immunity.

A tendency toward excessive inflammation in cystic fibrosis (CF) patients often accompanies lung infections with Pseudomonas aeruginosa. We tested the cytokine response to P. aeruginosa in two pairs of human airway epithelial cell lines matched except for CF transmembrane conductance regulator activity. The 9/HTEo(-) CF-phenotypic cell line produced significantly more interleukin (IL)-8, IL-6, and granulocyte-macrophage colony-stimulating factor but not regulated on activation normal T cell expressed and secreted (RANTES) in response to Pseudomonas than the 9/HTEo(-) control line, and the differences widened over time. Similarly, a 16HBE cell line lacking transmembrane conductance regulator activity showed enhanced IL-8 and IL-6 responses compared with the control cell line. The pharmacology of the cytokine response also differed because dexamethasone reduced cytokine production to similar levels in the matched cell lines. The protracted proinflammatory cytokine response of the CF-phenotypic cell lines suggests that the limiting mechanisms of normal cells are absent or attenuated. These results are consistent with in vivo observations in patients with CF and suggest that our novel cell lines may be useful for further investigation of the proinflammatory responses in CF airways.