Innate recognition of apoptotic cells: novel apoptotic cell-associated molecular patterns revealed by crossreactivity of anti-LPS antibodies

• Published in: Cell death and differentiation Vol. 20; no. 5; pp. 698 - 708
• Main Authors: Tennant, I, Pound, J D, Marr, L A, Willems, J J L P, Petrova, S, Ford, C A, Paterson, M, Devitt, A, Gregory, C D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2013; Nature Publishing Group
• Subjects: 631/250/262/2106; 631/61/51/1568; 631/80/82/23; 631/92/287/1190; Acute-Phase Proteins - immunology; Animals; Annexin A5 - metabolism; Antibodies, Monoclonal - immunology; Apoptosis; Apoptosis - immunology; Biochemistry; Biomedical and Life Sciences; Carrier Proteins - immunology; Cell Biology; Cell Cycle Analysis; Cell death; Cell Line; Chlorocebus aethiops; Complement C1q - metabolism; COS Cells; Epitopes - immunology; HEK293 Cells; Humans; Hypotheses; Immune system; Immunity, Innate; Laminin - metabolism; Life Sciences; Lipopolysaccharide Receptors; Lipopolysaccharides - immunology; Lymphoma; Medical research; Membrane Glycoproteins - immunology; Molecular Structure; Monoclonal antibodies; Original Paper; Pathogens; Pattern recognition; Proteins; Receptors, Pattern Recognition - immunology; Septins - immunology; Stem Cells; United Kingdom > UK; apoptosis; antibody; innate immunity; LPS; pattern recognition
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2012.165

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.