Pathological changes in inflammatory bowel disease include an increase in intestinal mucosal mononuclear leukocytes and hyperplasia of the muscularis mucosae smooth muscle cells (M-SMCs). Because virus infections have correlated with disease flare, we tested the response of cultured M-SMCs to respiratory syncytial virus, measles virus, and the viral analogue, poly(I·C). Adhesion of U937 cells and peripheral blood mononuclear cells was used to measure the leukocyte-interactive potential of M-SMCs. Untreated M- SMCs, only minimally adhesive for leukocytes, bound U937 cells after treatment with respiratory syncytial virus or measles virus. Mononuclear leukocytes also bound to poly(I·C)-treated M-SMCs. Although both vascular cell adhesion molecule-1 mRNA and protein increased 3-4-fold in poly(I·C)- treated M-SMC cultures, U937 cell adhesion was not blocked by an anti- vascular cell adhesion molecule-1 monoclonal antibody. However, hyaluronidase digestion of poly(I·C)- or virus-treated M-SMCs dramatically reduced leukocyte adhesion (~75%). Fluorophore-assisted carbohydrate electrophoresis demonstrated a ~3-fold increase in surface-bound hyaluronan on poly(I·C)- treated M-SMCs compared with untreated controls. In addition, pretreatment of mononuclear cells with a blocking anti-CD44 antibody, greatly decreased adhesion to poly(I·C)-treated M-SMCs. Recognition of this virus-induced hyaluronan/CD44 mechanism of mesenchymal cell/leukocyte interaction introduces a new avenue in the research of gut inflammation.
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