title: Fine particles that adsorb lipopolysaccharide via bridging calcium cations may mimic bacterial pathogenicity towards cells.
abstract: Fine particles (10(2)- to 10(3)-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-1beta (IL-1beta) 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-beta1 (TGF-beta1). 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-1beta 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.
authors.affiliation: Department of Medical Microbiology and Immunology and MIND Institute, University of California at Davis, Wet Lab Building, Sacramento, CA 95817, USA. pashwood@ucdavis.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Ashwood
authors.forename: Richard P H
authors.initials: RP
authors.lastname: Thompson
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Powell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000276:Adjuvants, Immunologic; D000327:Adsorption; D000328:Adult; D017209:Apoptosis; D002118:Calcium / Q000737:chemistry; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D014025:Titanium / Q000737:chemistry* / Q000276:immunology / Q000633:toxicity; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; C493277:MAPKAP1 protein, human; D017472:Receptors, Interleukin-1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D015638:Cytochalasin D; D014025:Titanium; D002118:Calcium