Mononuclear leukocytes preferentially bind via CD44 to hyaluronan on human intestinal mucosal smooth muscle cells after virus infection or treatment with poly(I.C).
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.
de La Motte
C A
CA
Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Hascall
V C
VC
Calabro
A
A
Yen-Lieberman
B
B
Strong
S A
SA
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
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