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ORIGINAL RESEARCH ARTICLE

Fine Particles That Adsorb Lipopolysaccharide Via Bridging Calcium Cations May Mimic Bacterial Pathogenicity Towards Cells

Paul Ashwood^*,1, Richard P. H. Thompson and Jonathan J. Powell

^* Department of Medical Microbiology and Immunology and M.I.N.D. Institute, University of California at Davis, Davis, California 95817; Gastrointestinal Laboratory, Rayne Institute, St. Thomas Hospital, London, United Kingdom; and MRC-Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL, United Kingdom

To whom requests for reprints should be addressed at ¹ Department of Medical Microbiology and Immunology and M.I.N.D. Institute, University of California at Davis, Wet Lab Building, 50th Street, Sacramento, CA 95817. E-mail: pashwood{at}ucdavis.edu

Fine particles (10²- to 10³-nm diameter) are potentially potent adjuvants in acquired immune responses but little is known about their interaction with pathogen-associated molecular patterns (PAMPs) and impact upon innate immunity. Here we show that 200-nm–sized, food-grade titanium dioxide avidly binds lipopolysaccharide (LPS) with bridging calcium cations, and the complex induces marked proinflammatory signalling in primary human mononuclear phagocytes. In particular, caspase 1-dependent interleukin-1ß (IL-1ß) secretion was induced at levels far greater than for the sum of the individual components, and without concomitant secretion of modulatory cytokines such as interleukin-1 receptor antagonist or transforming growth factor-ß1 (TGF-ß1). Secondly, the conjugate induced apoptotic-like cell death. These responses were inhibited by blockade of both phagocytosis and scavenger receptor uptake. Specific caspase 1–facilitated IL-1ß secretion and apoptosis following phagocytosis are features of cellular responses to certain invasive, enteric pathogens, and hence induction of these events may be mimicked by fine particle–LPS conjugates. The inadvertent adsorption of PAMPs to ingested, inhaled, or "wear" fine particulate matter provides a further potential mechanism for the proinflammatory nature of fine particles.

Key Words: fine particles • lipopolysaccharide • interleukin-1ß • apoptosis

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