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Toll-like receptor 2 is expressed by alveolar epithelial cells type II and macrophages in the human lung

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Abstract

The ability of the host to recognize pulmonary invasion by pathogenic organisms and establish an appropriate host response to infection requires innate immune defense mechanisms. Early bacterial clearance in the lung is mediated by alveolar macrophages (AM) and polymorphonuclear neutrophils. Additionally alveolar epithelial cells type II (AEC-II) may act as immunoregulatory cells. The toll-like receptors (TLR) are part of this innate immune defense, recognizing conserved patterns on microorganisms. Toll-like receptor 2 (TLR2) is crucial in detecting components of gram-positive bacteria and mycobacteria. Signals initiated by the interaction of TLR2 with bacterial components direct the subsequent inflammatory response. The detection of TLR2 mRNA in human lung tissue prompted us to localize the expression of mRNA and protein at the cellular level using a novel method for tissue fixation. We utilized HOPE-fixed lung specimen sections for targeting mRNA by in situ hybridization and protein by immunohistochemistry using the monoclonal antibody TL2.1. In normal lung areas the expression of TLR2 mRNA and protein was found to be located in cells resembling AEC-II and AM. Expression of mRNA was verified by RT-PCR and DNA sequencing. These results indicate a potential mechanism of increased immunosurveillance at the alveolar level controlling the localized infection.

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Fig. 1A–C.
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References

  • Diamond G, Legarda D, Ryan LK (2000) The innate immune response of the respiratory epithelium. Immunol Rev 173:27–38

    Article  CAS  PubMed  Google Scholar 

  • Fehrenbach H (2001) Alveolar epithelial type II cell: defender of the alveolus revisited. Respir Res 2:33–46

    CAS  PubMed  Google Scholar 

  • Flo TH, Halaas O, Lien E, Ryan L, Teti G, Golenbock DT, Sundan A, Espevik T (2000) Human toll-like receptor 2 mediates monocyte activation by Listeria monocytogenes, but not by group B streptococci or lipopolysaccharide. J Immunol 164:2064–2069

    CAS  PubMed  Google Scholar 

  • Flo TH, Halaas O, Torp S, Ryan L, Lien E, Dybdahl B, Sundan A, Espevik T (2001) Differential expression of toll-like receptor 2 in human cells. J Leukoc Biol 69:474–481

    CAS  PubMed  Google Scholar 

  • Goldmann T, Becher B, Wiedorn KH, Pirow R, Deutschbein ME, Vollmer E, Paul RJ (1999a) Epipodite and fat cells as sites of hemoglobin synthesis in the branchiopod crustacean Daphnia magna. Histochem Cell Biol 112:335–339

    Article  CAS  PubMed  Google Scholar 

  • Goldmann T, Suter L, Ribbert D, Otto F (1999b) The expression of proteolytic enzymes at the dermal invading front of primary cutaneous melanoma predicts metastasis. Pathol Res Pract 195:171–175

    CAS  PubMed  Google Scholar 

  • Goldmann T, Galle J, Wiedorn KH, Deutschbein ME, Neuhaus M, Branscheid D, Vollmer E (2001) Diagnostic value of immunohistochemically detected surfactant-apoprotein-A in malignant tumors located in the lungs: report of two cases. Ann Diagn Pathol 5:84–90

    Article  CAS  PubMed  Google Scholar 

  • Goldmann T, Wiedorn KH, Olert J, Branscheid D, Pechkovsky D, Zissel G, Galle J, Muller-Quernheim J, Vollmer E (2002) Assessment of transcriptional gene activity in situ by application of HOPE-fixed, paraffin-embedded tissues. Pathol Res Pract 198:91–95

    CAS  PubMed  Google Scholar 

  • Imler JL, Hoffmann JA (2001) Toll receptors in innate immunity. Trends Cell Biol 11:304–311

    Article  CAS  PubMed  Google Scholar 

  • Lien E, Ingalls RR (2002) Toll-like receptors. Crit Care Med 30:S1–S11

    CAS  Google Scholar 

  • Lien E, Sellati TJ, Yoshimura A, Flo TH, Rawadi G, Finberg RW, Carroll JD, Espevik T, Ingalls RR, Radolf JD, Golenbock DT (1999) Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products. J Biol Chem 274:33419–33425

    Article  CAS  PubMed  Google Scholar 

  • Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA (2000) A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect Immun 68:6398–6401

    Article  CAS  PubMed  Google Scholar 

  • Muzio M, Bosisio D, Polentarutti N, D'amico G, Stoppacciaro A, Mancinelli R, Veer C van't, Penton-Rol G, Ruco LP, Allavena P, Mantovani A (2000) Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 164:5998–6004

    CAS  PubMed  Google Scholar 

  • Olert J, Wiedorn KH, Goldmann T, Kühl H, Mehraein Y, Scherthan H, Niketeghad F, Vollmer E, Müller AM, Müller-Navia J (2001) HOPE-fixation: a novel fixing method and paraffin embedding technique for human soft tissues. Pathol Res Pract 197:823–826

    CAS  PubMed  Google Scholar 

  • Pechkovsky DV, Zissel G, Ziegenhagen MW, Einhaus M, Taube C, Rabe KF, Magnussen H, Papadopoulos T, Schlaak M, Muller-Quernheim J (2000) Effect of proinflammatory cytokines on interleukin-8 mRNA expression and protein production by isolated human alveolar epithelial cells type II in primary culture. Eur Cytokine Netw 11:618–625

    CAS  PubMed  Google Scholar 

  • Pechkovsky DV, Zissel G, Goldmann T, Einhaus M, Taube C, Magnussen H, Schlaak M, Muller-Quernheim J (2002) Pattern of NOS2 and NOS3 mRNA expression in human A549 and primary cultured AEC II. Am J Physiol Lung Cell Mol Physiol 282:L684–L692

    CAS  PubMed  Google Scholar 

  • Roche Molecular Biochemicals (1996) Nonradioactive in situ hybridization application manual, 2nd edn. Roche Diagnostics, Boehringer Mannheim, Mannheim, Germany

  • Rose F, Dahlem G, Guthmann B, Grimminger F, Maus U, Hanze J, Duemmer N, Grandel U, Seeger W, Ghofrani HA (2002) Mediator generation and signaling events in alveolar epithelial cells attacked by S. aureus alpha-toxin. Am J Physiol Lung Cell Mol Physiol 282:L207–L214

    CAS  PubMed  Google Scholar 

  • Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ (1999) Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem 274:17406–17409

    Article  CAS  PubMed  Google Scholar 

  • Sunil VR, Connor AJ, Guo Y, Laskin JD, Laskin DL (2002) Activation of type II alveolar epithelial cells during acute endotoxemia. Am J Physiol Lung Cell Mol Physiol 282:L872–L880

    CAS  PubMed  Google Scholar 

  • Takeuchi O, Hoshino K, Akira S (2000) Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J Immunol 165:5392–5396

    CAS  PubMed  Google Scholar 

  • Thoma-Uszynski S, Stenger S, Takeuchi O, Ochoa MT, Engele M, Sieling PA, Barnes PF, Rollinghoff M, Bolcskei PL, Wagner M, Akira S, Norgard MV, Belisle JT, Godowski PJ, Bloom BR, Modlin RL (2001) Induction of direct antimicrobial activity through mammalian toll-like receptors. Science 291:1544–1547

    Article  CAS  PubMed  Google Scholar 

  • Underhill DM, Ozinsky A, Smith KD, Aderem A (1999) Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci U S A 96:14459–14463

    CAS  PubMed  Google Scholar 

  • Visintin A, Mazzoni A, Spitzer JH, Wyllie DH, Dower SK, Segal DM (2001) Regulation of toll-like receptors in human monocytes and dendritic cells. J Immunol 166:249–255

    CAS  PubMed  Google Scholar 

  • Wolfs TG, Buurman WA, van Schadewijk A van, Vries B de, Daemen MA, Hiemstra PS, Veer C van 't (2002) In vivo expression of toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. J Immunol 168:1286–1293

    CAS  PubMed  Google Scholar 

  • Yang RB, Mark MR, Gray A, Huang A, Xie MH, Zhang M, Goddard A, Wood WI, Gurney AL, Godowski PJ (1998) Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature 395:284–288

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D (1999) Cutting edge: recognition of gram-positive bacterial cell wall components by the innate immune system occurs via toll-like receptor 2. J Immunol 163:1–5

    CAS  PubMed  Google Scholar 

  • Zarember KA, Godowski PJ (2002) Tissue expression of human toll-like receptors and differential regulation of toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J Immunol 168:554–561

    CAS  PubMed  Google Scholar 

  • Zhang P, Summer WR, Bagby GJ, Nelson S (2000) Innate immunity and pulmonary host defense. Immunol Rev 173:39–51

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr. G. Zissel, University Freiburg, Germany for providing the AEC-II culture, Dr. E. Richter, National Reference Center for Mycobacteria, Research Center Borstel, for sequencing the PCR products, and H. Kühl and W. Martens for excellent technical assistance.

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Authors and Affiliations

  1. Clinical and Experimental Pathology, Research Center Borstel, Parkallee 3, 23845, Borstel, Germany

    Torsten Goldmann, Ryan Clark & Ekkehard Vollmer

  2. Medical Clinic, Research Center Borstel, Parkallee 35, 23845, Borstel, Germany

    Daniel Droemann & Peter Zabel

  3. Medical Clinic III, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Klaus Dalhoff & Peter Zabel

  4. Department for Thoracic Surgery, Krankenhaus Grosshansdorf, Wöhrendamm 80, 22927, Grosshansdorf, Germany

    Detlev Branscheid

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  1. Daniel Droemann
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  2. Torsten Goldmann
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  3. Detlev Branscheid
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  4. Ryan Clark
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  5. Klaus Dalhoff
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  7. Ekkehard Vollmer
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Correspondence to Torsten Goldmann.

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Daniel Droemann and Torsten Goldmann are equal contributors

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Droemann, D., Goldmann, T., Branscheid, D. et al. Toll-like receptor 2 is expressed by alveolar epithelial cells type II and macrophages in the human lung. Histochem Cell Biol 119, 103–108 (2003). https://doi.org/10.1007/s00418-003-0497-4

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  • DOI: https://doi.org/10.1007/s00418-003-0497-4

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