Abstract
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-1β (IL-1β) 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-β1 (TGF-β1). 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-1β 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 107-117 |
| Number of pages | 11 |
| Journal | Experimental Biology and Medicine |
| Volume | 232 |
| Issue number | 1 |
| State | Published - Jan 2007 |
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Keywords
- Apoptosis
- Fine particles
- Interleukin-1β
- Lipopolysaccharide
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Fine particles that adsorb lipopolysaccharide via bridging calcium cations may mimic bacterial pathogenicity towards cells. / Ashwood, Paul; Thompson, Richard P H; Powell, Jonathan J.
In: Experimental Biology and Medicine, Vol. 232, No. 1, 01.2007, p. 107-117.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fine particles that adsorb lipopolysaccharide via bridging calcium cations may mimic bacterial pathogenicity towards cells
AU - Ashwood, Paul
AU - Thompson, Richard P H
AU - Powell, Jonathan J.
PY - 2007/1
Y1 - 2007/1
N2 - 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-1β (IL-1β) 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-β1 (TGF-β1). 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-1β 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.
AB - 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-1β (IL-1β) 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-β1 (TGF-β1). 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-1β 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.
KW - Apoptosis
KW - Fine particles
KW - Interleukin-1β
KW - Lipopolysaccharide
UR - http://www.scopus.com/inward/record.url?scp=33846139620&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846139620&partnerID=8YFLogxK
M3 - Article
C2 - 17202591
AN - SCOPUS:33846139620
VL - 232
SP - 107
EP - 117
JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
SN - 1535-3702
IS - 1
ER -