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Expression of Functional Toll-Like Receptor-2 and -4 on Alveolar Epithelial Cells

Lung Research Group, and Academic Renal Unit, Department of Clinical Science North Bristol, University of Bristol, Southmead Hospital, Westbury on Trym, Bristol; Department of Respiratory Medicine, Bristol Royal Infirmary, Bristol; and Respiratory Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Charing Cross Hospital, London, United Kingdom

Address correspondence to: Dr. Lynne Armstrong, Lung Research Group, University of Bristol, Department of Clinical Science North Bristol, Southmead Hospital, Westbury on Trym, Bristol BS10 5NB, UK. E-mail: lynne.armstrong{at}bris.ac.uk

The recognition of potentially harmful microorganisms involves the specific recognition of pathogen-associated molecular patterns (PAMPs) and the family of Toll-like receptors (TLRs) is known to play a central role in this process. TLR-4 is the major recognition receptor for lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, whereas TLR-2 responds to bacterial products from gram-positive organisms. Although resident alveolar macrophages are the first line of defense against microbial attack, it is now understood that the alveolar epithelium also plays a pivotal role in the innate immunity of the lung. The purpose of the current study was to determine whether human primary type II alveolar epithelial cells (ATII) express functional TLR-2 and TLR-4 and how they may be regulated by inflammatory mediators. We have used reverse transcriptase–polymerase chain reaction and flow cytometry to determine basal and inducible expression on ATII. We have used highly purified preparations of the gram-positive bacterial product lipoteichoic acid (LTA) and LPS to look at the functional consequences of TLR-2 and TLR-4 ligation, respectively, in terms of interleukin-8 release. We have shown that human primary ATII cells express mRNA and protein for both TLR-2 and TLR-4, which can be modulated by incubation with LPS and tumor necrosis factor. Furthermore, we have demonstrated that these receptors are functional. This suggests that ATII have the potential to contribute significantly to the host defense of the human alveolus against bacteria.

Abbreviations: aquaporin, AQP • alveolar type II epithelial cells, ATII • glyceraldehyde-3-phosphate dehydrogenase, GAPDH • Hanks' balanced salt solution, HBSS • interferon, IFN • immunoglobulin, IgG • interleukin, IL • lipoteichoic acid, LTA • lipopolysaccharide, LPS • pathogen-associated molecular patterns, PAMPs • phosphate-buffered saline, PBS • phycoerythrin, Pe • repurified lipopolysaccharide, rLPS • reverse transcriptase polymerase chain reaction, RT-PCR • surfactant protein C, SP-C • Toll-like receptor, TLR • tumor necrosis factor-, TNF-

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