title: Adherent human alveolar macrophages exhibit a transient pro-inflammatory profile that confounds responses to innate immune stimulation.
abstract: Alveolar macrophages (AM) are thought to have a key role in the immunopathogenesis of respiratory diseases. We sought to test the hypothesis that human AM exhibit an anti-inflammatory bias by making genome-wide comparisons with monocyte derived macrophages (MDM). Adherent AM obtained by bronchoalveolar lavage of patients under investigation for haemoptysis, but found to have no respiratory pathology, were compared to MDM from healthy volunteers by whole genome transcriptional profiling before and after innate immune stimulation. We found that freshly isolated AM exhibited a marked pro-inflammatory transcriptional signature. High levels of basal pro-inflammatory gene expression gave the impression of attenuated responses to lipopolysaccharide (LPS) and the RNA analogue, poly IC, but in rested cells pro-inflammatory gene expression declined and transcriptional responsiveness to these stimuli was restored. In comparison to MDM, both freshly isolated and rested AM showed upregulation of MHC class II molecules. In most experimental paradigms ex vivo adherent AM are used immediately after isolation. Therefore, the confounding effects of their pro-inflammatory profile at baseline need careful consideration. Moreover, despite the prevailing view that AM have an anti-inflammatory bias, our data clearly show that they can adopt a striking pro-inflammatory phenotype, and may have greater capacity for presentation of exogenous antigens than MDM.
authors: Infection and Immunity, University College London, London, United Kingdom.
authors: Gillian S
authors: GS
authors: Tomlinson
authors: Helen
authors: H
authors: Booth
authors: Sarah J
authors: SJ
authors: Petit
authors: Elspeth
authors: E
authors: Potton
authors: Greg J
authors: GJ
authors: Towers
authors: Robert F
authors: RF
authors: Miller
authors: Benjamin M
authors: BM
authors: Chain
authors: Mahdad
authors: M
authors: Noursadeghi
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002469:Cell Separation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D014157:Transcription Factors