Moraxella catarrhalis lipooligosaccharide selectively upregulates ICAM-1 expression on human monocytes and stimulates adjacent naïve monocytes to produce TNF-alpha through cellular cross-talk.
To elucidate the role of Moraxella catarrhalis lipooligosaccharide (LOS) in otitis media with effusion (OME), the effects of LOS on adhesion antigens of human monocytes were investigated. M. catarrhalis LOS selectively enhanced intercellular adhesion molecule 1 (ICAM-1 or CD54) expression on human monocytes by significantly increasing both the surface expression intensity and the percentage of ICAM-1(+) cells. ICAM-1 upregulation on human monocytes by the LOS required surface CD14, TLR4, NF-kappaB p65 and c-Jun N-terminal kinase (JNK) activity. Our study also revealed that the LOS-induced surface ICAM-1 expression was partially mediated through a TNF-alpha dependent autocrine mechanism and could be further augmented by lipopolysaccharide-binding protein in serum. In addition, M. catarrhalis LOS also stimulated human monocytes to produce pro-inflammatory cytokines in both TLR4- and CD14-dependent pathways. Our results also indicated that enhanced surface ICAM-1 expression on monocytes may hinder their adherence to the lung epithelial monolayer. Furthermore, the LOS-activated human monocytes secreted a significantly high level of IL-8, and could stimulate adjacent naïve monocytes to produce TNF-alpha which was partially mediated via membrane ICAM-1 and IL-8/IL-8RA. These results suggest that M. catarrhalis LOS could induce excessive middle ear inflammation through a cellular cross-talk mechanism during OME.
Xie
Hang
H
Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
Gu
Xin-Xing
XX
D000209:Acute-Phase Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D001936:Moraxella catarrhalis / Q000737:chemistry / Q000276:immunology* / Q000472:pathogenicity; D010034:Otitis Media with Effusion / Q000276:immunology / Q000382:microbiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018799:Intercellular Adhesion Molecule-1; D016209:Interleukin-8; D048031:JNK Mitogen-Activated Protein Kinases; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C495345:TLR4 protein, human; C023023:lipid-linked oligosaccharides