Inflammatory cytokines can enhance CD44-mediated airway epithelial cell adhesion independently of CD44 expression.
In airways, the cell surface molecule CD44 is upregulated on bronchial epithelial cells in areas of damage. We have shown that a blocking standard CD44 (CD44s) antibody caused a 77% (+/- 19%) inhibition of cell migration at 3 h after mechanical damage and decreased epithelial cell repair of cells grown on cell culture filter inserts. With the use of primary human bronchial epithelial cells and the bronchial epithelial cell line 16HBE 14o-, a CD44s antibody inhibited >95% (P < 0.01) of cell binding to hyaluronic acid (HA). The cytokines TNF-alpha, IFN-gamma, IL-1 beta, and IL-4 stimulated a 2- to 3.5-fold increase in CD44-dependent cell binding to HA. IFN-gamma treatment did not increase CD44 expression as assessed by flow cytometry, although phorbol myristate acetate treatment did. This indicates that IFN-gamma-induced cell binding to HA did not require increased CD44 expression. These data indicate that CD44 is important for bronchial epithelial cell binding to HA and that cytokines known to be expressed in inflammation can increase HA binding independently of the level of CD44 expression.
Leir
Shih-Hsing
SH
Respiratory Cell and Molecular Biology, Infection Immunity and Repair Division, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
Holgate
Stephen T
ST
Lackie
Peter M
PM
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000502:physiology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000166:cytology*; D015854:Up-Regulation / Q000276:immunology; D014945:Wound Healing / Q000276:immunology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000970:Antineoplastic Agents; D018960:Hyaluronan Receptors; D007371:Interferon-gamma; D006820:Hyaluronic Acid