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

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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.

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  • Innate recognition of apoptotic cells

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Details

Original languageEnglish
Pages (from-to)698-708
Number of pages11
JournalCell Death and Differentiation
Volume20
Issue number5
Early online date12 Feb 2013
DOIs
Publication statusPublished - 8 May 2013

Bibliographic note

Funding: Leukaemia and Lymphoma Research; Medical Research Council (UK). Authors of research articles can also opt to pay an article processing charge (in addition to the standard publication charges) for their accepted articles to be open access online and freely accessible, immediately upon publication. By paying this charge authors are also permitted to post the final, published PDF of their article on a website, institutional repository or other free public server, immediately on publication. Open Access articles can be published under a Creative Commons Attribution 3.0 Unported License at the free choice of the authors. [In article Copyright: 2013 Macmillan Publishers Limited] Supplementary Information accompanies this paper on Cell Death and Differentiation website (http://www.nature.com/cdd)

    Keywords

  • antibody, apoptosis, innate immunity, LPS, pattern recognition

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