title: Innate recognition of apoptotic cells: novel apoptotic cell-associated molecular patterns revealed by crossreactivity of anti-LPS antibodies.
abstract: Cells dying by apoptosis are normally cleared by phagocytes through mechanisms that can suppress inflammation and immunity. Molecules of the innate immune system, the pattern recognition receptors (PRRs), are able to interact not only with conserved structures on microbes (pathogen-associated molecular patterns, PAMPs) but also with ligands displayed by apoptotic cells. We reasoned that PRRs might therefore interact with structures on apoptotic cells - apoptotic cell-associated molecular patterns (ACAMPs) - that are analogous to PAMPs. Here we show that certain monoclonal antibodies raised against the prototypic PAMP, lipopolysaccharide (LPS), can crossreact with apoptotic cells. We demonstrate that one such antibody interacts with a constitutively expressed intracellular protein, laminin-binding protein, which translocates to the cell surface during apoptosis and can interact with cells expressing the prototypic PRR, mCD14 as well as with CD14-negative cells. Anti-LPS cross reactive epitopes on apoptotic cells colocalised with annexin V- and C1q-binding sites on vesicular regions of apoptotic cell surfaces and were released associated with apoptotic cell-derived microvesicles (MVs). These results confirm that apoptotic cells and microbes can interact with the immune system through common elements and suggest that anti-PAMP antibodies could be used strategically to characterise novel ACAMPs associated not only with apoptotic cells but also with derived MVs.
authors: Medical Research Council MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors: I
authors: I
authors: Tennant
authors: J D
authors: JD
authors: Pound
authors: L A
authors: LA
authors: Marr
authors: J J L P
authors: JJ
authors: Willems
authors: S
authors: S
authors: Petrova
authors: C A
authors: CA
authors: Ford
authors: M
authors: M
authors: Paterson
authors: A
authors: A
authors: Devitt
authors: C D
authors: CD
authors: Gregory
mesh_terms: D000209:Acute-Phase Proteins / Q000276:immunology; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D019556:COS Cells; D002352:Carrier Proteins / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D015922:Complement C1q / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D007797:Laminin / Q000378:metabolism; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D015394:Molecular Structure; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D058112:Septins / Q000276:immunology; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D017304:Annexin A5; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D015922:Complement C1q; D000939:Epitopes; D007797:Laminin; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D051192:Receptors, Pattern Recognition; D058112:Septins; D000099231:Lipopolysaccharide-Binding Protein; C000602252:SEPTIN2 protein, human
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