NKG2D ligands are expressed on stressed human airway epithelial cells.
Immune surveillance of the airways is critical to maintain the integrity and health of the lung. We have identified a family of ligands expressed on the surface of stressed airway epithelial cells whose function is to bind the NKG2D-activating receptor found on several pulmonary lymphocytes, including natural killer cells, gammadelta(+) T cells, and CD8(+) T cells. We employed real-time PCR and flow cytometry in normal and transformed airway epithelial cell to demonstrate that major histocompatibility complex class I chain-related (MIC) B and the UL-16 binding protein (ULBP) ligands (ULBP1-4) are ubiquitously expressed at the mRNA level in all cell lines. MICA/B surface expression was present on 70% of transformed cell lines but was undetectable on primary cells. We demonstrate that MICA/B and ULBP 1, 2, 3, and 4 expression is rare or absent on the cell surface of unstimulated normal human bronchial epithelial cells although transcripts and intracellular proteins are present. Normal human bronchial epithelial cells exposed to 0.3 mM hydrogen peroxide exhibit an induction of all ligands examined on the cell surface. Surface expression is independent of changes in transcript level or total cellular protein and is mediated by the ERK family of mitogen-activated protein kinases. The induction of NKG2D ligands on stressed airway epithelial cells represents a potentially important mechanism of immune cell activation in regulation of pulmonary health and disease.
Department of Environmental Health, Division of Environmental Genetics and Molecular Toxicology, University of Cincinnati College of Medicine, OH 45267, USA. michael.borchers@uc.edu
Michael T
MT
Borchers
Nathaniel L
NL
Harris
Scott C
SC
Wesselkamper
Mark
M
Vitucci
David
D
Cosman
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism
D002352:Carrier Proteins; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D008024:Ligands; C099187:MHC class I-related chain A; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016877:Oxidants; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C423231:ULBP1 protein, human; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases