title: Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells.
abstract: 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.
authors.affiliation: Lung Research Group, University of Bristol, Department of Clinical Science North Bristol, Southmead Hospital, Westbury on Trym, Bristol BS10 5NB, UK. lynne.armstrong@bris.ac.uk
authors.forename: Lynne
authors.initials: L
authors.lastname: Armstrong
authors.forename: Andrew R L
authors.initials: AR
authors.lastname: Medford
authors.forename: Kay M
authors.initials: KM
authors.lastname: Uppington
authors.forename: John
authors.initials: J
authors.lastname: Robertson
authors.forename: Ian R
authors.initials: IR
authors.lastname: Witherden
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
authors.forename: Ann B
authors.initials: AB
authors.lastname: Millar
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D017931:DNA Primers; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors