The present study was designed to investigate the effects of the bacterial toxins lipopolysaccharide (LPS) and lipoteichoic acid (LTA) on air-exposed cultured human respiratory sinus epithelium. The morphological changes, proliferation, and differentiation of sphenoid sinus mucosa were examined after incubation with different LPS or LTA concentrations. Air-exposed cultured sinus mucosa differentiated from pseudostratified respiratory epithelium to squamous ciliated epithelium with few goblet cells. High concentrations of bacterial toxins induced a significant increase in mucus production and a decrease in ciliated cells. Ki67 immunostaining showed an increased cell proliferation after incubation with moderate levels of LPS or LTA. High concentrations of bacterial toxins, on the other hand, induced a decreased proliferation. Involucrin expression was clearly altered by incubation with high levels of bacterial toxins, indicating an increased degree of terminal differentiation. These results indicate that the bacterial toxins LPS and LTA both induce comparable dose-dependent morphological changes in sinus epithelium.
Al-RawiMMEdelsteinDRErlandsonRA. Changes in nasal epithelium in patients with severe chronic sinusitis: A clinicopathologic and electron microscopic study. Laryngoscope1998;108:1816–23.
2.
NorlanderTWestrinKMStiernaP. The inflammatory response of the sinus and nasal mucosa during sinusitis: Implications for research and therapy. Acta Otolaryngol Suppl (Stockh)1994(suppl 515):38–44.
3.
HarkemaJRHotchkissJA. Ozone- and endotoxin-induced mucous cell metaplasias in rat airway epithelium: Novel animal models to study toxicant-induced epithelial transformation in airways. Toxicol Lett1993;68:251–63.
4.
WilsonRDowlingRBJacksonAD. The biology of bacterial colonization and invasion of the respiratory mucosa. Eur Respir J1996;9:1523–30.
ShimizuTTakahashiYTakeuchiKMajimaYSakakuraY. Role of neutrophil elastase in endotoxin-induced mucus hypersecretion in rat nasal epithelium. Ann Otol Rhinol Laryngol2000;109:1049–54.
7.
SuzukiKNishiyamaYSugiyamaKMiyamotoNBabaS. Recent trends in clinical isolates from paranasal sinusitis. Acta Otolaryngol Suppl (Stockh)1996(suppl 525):51–5.
8.
OhashiYNakaiYEsakiYOhnoYSugiuraYOkamotoH. Experimental otitis media with effusion induced by lipopolysaccharide from Klebsiella pneumoniae. Mucociliary pathology of the eustachian tube. Acta Otolaryngol Suppl (Stockh)1991(suppl 486):105–15.
9.
HunterSESinglaAKPrazmaJJewettBSRandellSHPillsburyHCIII. Mucin production in the middle ear in response to lipopolysaccharides. Otolaryngol Head Neck Surg1999; 120: 884–8.
10.
YanagiharaKSekiMChengP-W. Lipopolysaccharide induces mucus cell metaplasia in mouse lung. Am J Respir Cell Mol Biol2001;24:66–73.
11.
NellMJOp't HofBMKoertenHKGroteJJ. Effect of endotoxin on cultured human middle ear epithelium. ORL J Otorhinolaryngol Relat Spec1999;61:201–5.
12.
NellMJGroteJJ. Structural changes in the rat middle ear mucosa due to endotoxin and eustachian tube obstruction. Eur Arch Otorhinolaryngol1999;256:167–72.
13.
SriskandanSCohenJ. Gram-positive sepsis. Mechanisms and differences from gram-negative sepsis. Infect Dis Clin North Am1999;13:397–412.
14.
KitaHHimiT. Cytokine and chemokine induction using cell wall component and toxin derived from gram-positive bacteria in the rat middle ear. Acta Otolaryngol (Stockh)1999; 119: 446–52.
15.
PöllänenMTSalonenJIGrenierDUittoVJ. Epithelial cell response to challenge of bacterial lipoteichoic acids and lipopolysaccharides in vitro. J Med Microbiol2000;49:245–52.
16.
BoekWMGraamansKHuizingEH. Ciliary beat frequency of human sphenoid mucosa after cryopreservation. Eur Arch Otorhinolaryngol1997;255:135–7.
17.
HazelbagHMvan den BroekLJvan DorstEBOffer-HausGJPleurenGJHogendoornPC. Immunostaining of chain-specific keratins on formalin-fixed, paraffin-embedded tissues: A comparison of various antigen retrieval systems using microwave heating and proteolytic pre-treatments. J Histochem Cytochem1995;43:429–37.
18.
UsuiSShimizuTKishiokaCFujitaKSakakuraY. Secretory cell differentiation and mucus secretion in cultures of human nasal epithelial cells: Use of a monoclonal antibody to study human nasal mucin. Ann Otol Rhinol Laryngol2000; 109:271–7.
19.
SakakuraYMajimaYSaidaSUkaiKMiyoshiY. Reversibility of reduced mucociliary clearance in chronic sinusitis. Clin Otolaryngol1985;10:79–83.
20.
OhtaYIchimuraK. Proliferation markers, proliferating cell nuclear antigen, Ki67,5-bromo-2′-deoxyuridine, and cyclin D1 in mouse olfactory epithelium. Ann Otol Rhinol Laryngol2000;109:1046–8.
21.
HesselingSCvan BlitterswijkCALimDJDeMariaTFBakaletzLOGroteJJ. Effect of endotoxin on cultured rat middle ear epithelium, rat meatal epidermis, and human keratinocytes. Am J Otol1994;15:762–8.
22.
RakicJ-MGalandAVrensenGFJM. Lens epithelial cell proliferation in human posterior capsule opacification specimens. Exp Eye Res2000;71:489–94.
23.
SaidJWNashGSassoonAFShintakuIPBanks-SchlegelS. Involucrin in lung tumors. A specific marker for squamous differentiation. Lab Invest1983;49:563–8.
24.
MoriyamaTAsahinaIIshiiMOdaMIshiiYEnomotoS. Development of composite cultured oral mucosa utilizing collagen sponge matrix and contracted collagen gel: A preliminary study for clinical applications. Tissue Eng2001;7: 415–27.
25.
Banks-SchlegelSGreenH. Involucrin synthesis and tissue assembly by keratinocytes in natural and cultured human epithelia. J Cell Biol1981;90:732–7.
26.
ThomasGA. The immunohistochemical detection of involucrin in denture induced fibrous inflammatory hyperplasia of oral mucous membrane. Aust Prosthodont J1991;5:29–34.
27.
HarkemaJRHotchkissJA. In vivo effects of endotoxin on nasal epithelial mucosubstances: Quantitative histochemistry. Exp Lung Res1991;17:743–61.
28.
KrutzikSRSielingPAModlinRL. The role of Tolllike receptors in host defense against microbial infection. Curr Opin Immunol2001; 13:104–8.
29.
MedzhitovRJanewayCJr. The Toll receptor family and microbial recognition. Trends Microbiol2000;8:452–6.
30.
AndersonKV. Toll signaling pathways in the innate immune response. Curr Opin Immunol2000;12:13–9.
