title: Mononuclear leukocytes preferentially bind via CD44 to hyaluronan on human intestinal mucosal smooth muscle cells after virus infection or treatment with poly(I.C).
abstract: 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 ( approximately 75%). Fluorophore-assisted carbohydrate electrophoresis demonstrated a approximately 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.
authors.affiliation: Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: de La Motte
authors.forename: V C
authors.initials: VC
authors.lastname: Hascall
authors.forename: A
authors.initials: A
authors.lastname: Calabro
authors.forename: B
authors.initials: B
authors.lastname: Yen-Lieberman
authors.forename: S A
authors.initials: SA
authors.lastname: Strong
mesh_terms: D015703:Antigens, CD / Q000502:physiology; D002448:Cell Adhesion; D002478:Cells, Cultured; D003106:Colon; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology* / Q000821:virology*; D008459:Measles virus / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000502:physiology
chemical_list: D015703:Antigens, CD; D018960:Hyaluronan Receptors; D016898:Interferon-alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D007371:Interferon-gamma; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase; D011070:Poly I-C