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Implication of scavenger receptors in the interactions between diesel exhaust particles and immature or mature dendritic cells.

Taront S, Dieudonné A, Blanchard S, Jeannin P, Lassalle P, Delneste Y, Gosset P - Part Fibre Toxicol (2009)

Bottom Line: However, the mechanisms by which DEP have an effect on human health are not completely understood.Our data demonstrate that TLR2 agonists mainly augmented CXCL16, LOX-1 and SR-B1 expression whereas DEP alone had only a weak effect.In contrast, the decrease of IL-12 and CXCL10 secretion and the generation of oxygen metabolite induced by DEP at 10 mug/ml was not affected by SR ligands Our results show for the first time that the modulation of DC functions by DEP implicates SR.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM, U774, Lille, F-59019, France; Institut Pasteur de Lille, Lille, F-59019, France; Univ Lille II, Lille, F-59000 France. Philippe.Gosset@pasteur-lille.fr.

ABSTRACT

Background: The exposure to pollutants such as diesel exhaust particles (DEP) is associated with an increased incidence of respiratory diseases. However, the mechanisms by which DEP have an effect on human health are not completely understood. In addition to their action on macrophages and airway epithelial cells, DEP also modulate the functions of dendritic cells (DC). These professional antigen-presenting cells are able to discriminate unmodified self from non-self thanks to pattern recognition receptors such as the Toll like Receptors (TLR) and Scavenger Receptors (SR). SR were originally identified by their ability to bind and internalize modified lipoproteins and microorganisms but also particles and TLR agonists. In this study, we assessed the implication of SR in the effects of DEP associated or not with TLR agonists on monocyte-derived DC (MDDC). For this, we studied the regulation of CD36, CXCL16, LOX-1, SR-A1 and SR-B1 expression on MDDC treated with DEP associated or not with TLR2, 3 and 4 ligands. Then, the capacity of SR ligands (dextran sulfate and maleylated-ovalbumin) to block the effects of DEP on the function of lipopolysaccharide (LPS)-activated DC has been evaluated.

Results: Our data demonstrate that TLR2 agonists mainly augmented CXCL16, LOX-1 and SR-B1 expression whereas DEP alone had only a weak effect. Interestingly, DEP modulated the action of TLR2 and TLR4 ligands on the expression of LOX-1 and SR-B1. Pretreatment with the SR ligand maleylated-ovalbumin but not dextran sulfate inhibited the endocytosis of DEP by MDDC. Moreover, this SR ligand blocked the effect by DEP at low dose (1 mug/ml) on MDDC phenotype (a decrease of CD86 and HLA-DR expression) and on the secretion of CXCL10, IL-12 and TNF-alpha. In contrast, the decrease of IL-12 and CXCL10 secretion and the generation of oxygen metabolite induced by DEP at 10 mug/ml was not affected by SR ligands

Conclusion: Our results show for the first time that the modulation of DC functions by DEP implicates SR. TLR agonists upregulated SR expression in contrast to DEP. Interfering with the expression and/or the function of SR might be one way to limit the impact of DEP on lung immune response.

No MeSH data available.


Related in: MedlinePlus

DEP and PAMP modulate protein expression of Scavenger Receptors in MDDC. MDDC were cultivated with TLR2, -3 and -4 ligands respectively Pam3CSK4 (10 μg/ml), poly(I:C) (10 μg/ml) and LPS (1 μg/ml), associated or not with DEP (10 μg/ml). A-B Dendritic cells activated during 6 h (A) and 24 h (B) were labelled for CD36, CXCL16, LOX-1 and SR-B1, and analyzed by flow cytometry. Data are expressed as the mean ± SEM from 3 to 7 independent experiments. +: p < 0.05; ++: p < 0.01 compared with unstimulated cells. ✻: p < 0,05 compared with TLR-treated cells. C-D Flow cytometry histograms of a representative experiment. MDDC were cultivated for 6 h (C) and 24 h (D) with DEP (blue line), with TLR2 ligand (Pam3CSK4, red line), and with both stimuli (green line) as compared with cells in medium alone (black line).
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Figure 3: DEP and PAMP modulate protein expression of Scavenger Receptors in MDDC. MDDC were cultivated with TLR2, -3 and -4 ligands respectively Pam3CSK4 (10 μg/ml), poly(I:C) (10 μg/ml) and LPS (1 μg/ml), associated or not with DEP (10 μg/ml). A-B Dendritic cells activated during 6 h (A) and 24 h (B) were labelled for CD36, CXCL16, LOX-1 and SR-B1, and analyzed by flow cytometry. Data are expressed as the mean ± SEM from 3 to 7 independent experiments. +: p < 0.05; ++: p < 0.01 compared with unstimulated cells. ✻: p < 0,05 compared with TLR-treated cells. C-D Flow cytometry histograms of a representative experiment. MDDC were cultivated for 6 h (C) and 24 h (D) with DEP (blue line), with TLR2 ligand (Pam3CSK4, red line), and with both stimuli (green line) as compared with cells in medium alone (black line).

Mentions: We next determined by flow cytometry the effect of these stimuli on SR membrane expression in MDDC activated during 6 and 24 h. At the opposite of the mRNA expression, DEP alone significantly decreased after 6 h stimulation the expression of CD36 (p < 0.05) and SR-B1 (p = NS) whereas it did not affect the level of CXCL16 and LOX-1 (Fig 3A and 3C). TLR2 ligand significantly increased the expression of LOX-1 after 6 h stimulation (p < 0.05) and CXCL16 and SR-B1 after 24 h stimulation (p < 0.05) whereas it significantly decreased the expression of CD36 after 24 h stimulation (p < 0.05) (Fig 3A–D). The activation by TLR3 agonist only tended to increase CXCL16 expression after 24 h. The TLR4 ligand increased LOX-1 after 24 h stimulation, whereas it significantly decreased the expression of CD36 after 24 h stimulation (p < 0.05). The effect of TLR2 agonist was illustrated in figure 3C–D by histograms of flow cytometry from a representative experiment. In contrast with the effect of LPS and poly(IC), the TLR2 agonist significantly decreased the expression of SR-A1 after 24 h activation (Fig 2B) but not after 6 h (data not shown).


Implication of scavenger receptors in the interactions between diesel exhaust particles and immature or mature dendritic cells.

Taront S, Dieudonné A, Blanchard S, Jeannin P, Lassalle P, Delneste Y, Gosset P - Part Fibre Toxicol (2009)

DEP and PAMP modulate protein expression of Scavenger Receptors in MDDC. MDDC were cultivated with TLR2, -3 and -4 ligands respectively Pam3CSK4 (10 μg/ml), poly(I:C) (10 μg/ml) and LPS (1 μg/ml), associated or not with DEP (10 μg/ml). A-B Dendritic cells activated during 6 h (A) and 24 h (B) were labelled for CD36, CXCL16, LOX-1 and SR-B1, and analyzed by flow cytometry. Data are expressed as the mean ± SEM from 3 to 7 independent experiments. +: p < 0.05; ++: p < 0.01 compared with unstimulated cells. ✻: p < 0,05 compared with TLR-treated cells. C-D Flow cytometry histograms of a representative experiment. MDDC were cultivated for 6 h (C) and 24 h (D) with DEP (blue line), with TLR2 ligand (Pam3CSK4, red line), and with both stimuli (green line) as compared with cells in medium alone (black line).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2657891&req=5

Figure 3: DEP and PAMP modulate protein expression of Scavenger Receptors in MDDC. MDDC were cultivated with TLR2, -3 and -4 ligands respectively Pam3CSK4 (10 μg/ml), poly(I:C) (10 μg/ml) and LPS (1 μg/ml), associated or not with DEP (10 μg/ml). A-B Dendritic cells activated during 6 h (A) and 24 h (B) were labelled for CD36, CXCL16, LOX-1 and SR-B1, and analyzed by flow cytometry. Data are expressed as the mean ± SEM from 3 to 7 independent experiments. +: p < 0.05; ++: p < 0.01 compared with unstimulated cells. ✻: p < 0,05 compared with TLR-treated cells. C-D Flow cytometry histograms of a representative experiment. MDDC were cultivated for 6 h (C) and 24 h (D) with DEP (blue line), with TLR2 ligand (Pam3CSK4, red line), and with both stimuli (green line) as compared with cells in medium alone (black line).
Mentions: We next determined by flow cytometry the effect of these stimuli on SR membrane expression in MDDC activated during 6 and 24 h. At the opposite of the mRNA expression, DEP alone significantly decreased after 6 h stimulation the expression of CD36 (p < 0.05) and SR-B1 (p = NS) whereas it did not affect the level of CXCL16 and LOX-1 (Fig 3A and 3C). TLR2 ligand significantly increased the expression of LOX-1 after 6 h stimulation (p < 0.05) and CXCL16 and SR-B1 after 24 h stimulation (p < 0.05) whereas it significantly decreased the expression of CD36 after 24 h stimulation (p < 0.05) (Fig 3A–D). The activation by TLR3 agonist only tended to increase CXCL16 expression after 24 h. The TLR4 ligand increased LOX-1 after 24 h stimulation, whereas it significantly decreased the expression of CD36 after 24 h stimulation (p < 0.05). The effect of TLR2 agonist was illustrated in figure 3C–D by histograms of flow cytometry from a representative experiment. In contrast with the effect of LPS and poly(IC), the TLR2 agonist significantly decreased the expression of SR-A1 after 24 h activation (Fig 2B) but not after 6 h (data not shown).

Bottom Line: However, the mechanisms by which DEP have an effect on human health are not completely understood.Our data demonstrate that TLR2 agonists mainly augmented CXCL16, LOX-1 and SR-B1 expression whereas DEP alone had only a weak effect.In contrast, the decrease of IL-12 and CXCL10 secretion and the generation of oxygen metabolite induced by DEP at 10 mug/ml was not affected by SR ligands Our results show for the first time that the modulation of DC functions by DEP implicates SR.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM, U774, Lille, F-59019, France; Institut Pasteur de Lille, Lille, F-59019, France; Univ Lille II, Lille, F-59000 France. Philippe.Gosset@pasteur-lille.fr.

ABSTRACT

Background: The exposure to pollutants such as diesel exhaust particles (DEP) is associated with an increased incidence of respiratory diseases. However, the mechanisms by which DEP have an effect on human health are not completely understood. In addition to their action on macrophages and airway epithelial cells, DEP also modulate the functions of dendritic cells (DC). These professional antigen-presenting cells are able to discriminate unmodified self from non-self thanks to pattern recognition receptors such as the Toll like Receptors (TLR) and Scavenger Receptors (SR). SR were originally identified by their ability to bind and internalize modified lipoproteins and microorganisms but also particles and TLR agonists. In this study, we assessed the implication of SR in the effects of DEP associated or not with TLR agonists on monocyte-derived DC (MDDC). For this, we studied the regulation of CD36, CXCL16, LOX-1, SR-A1 and SR-B1 expression on MDDC treated with DEP associated or not with TLR2, 3 and 4 ligands. Then, the capacity of SR ligands (dextran sulfate and maleylated-ovalbumin) to block the effects of DEP on the function of lipopolysaccharide (LPS)-activated DC has been evaluated.

Results: Our data demonstrate that TLR2 agonists mainly augmented CXCL16, LOX-1 and SR-B1 expression whereas DEP alone had only a weak effect. Interestingly, DEP modulated the action of TLR2 and TLR4 ligands on the expression of LOX-1 and SR-B1. Pretreatment with the SR ligand maleylated-ovalbumin but not dextran sulfate inhibited the endocytosis of DEP by MDDC. Moreover, this SR ligand blocked the effect by DEP at low dose (1 mug/ml) on MDDC phenotype (a decrease of CD86 and HLA-DR expression) and on the secretion of CXCL10, IL-12 and TNF-alpha. In contrast, the decrease of IL-12 and CXCL10 secretion and the generation of oxygen metabolite induced by DEP at 10 mug/ml was not affected by SR ligands

Conclusion: Our results show for the first time that the modulation of DC functions by DEP implicates SR. TLR agonists upregulated SR expression in contrast to DEP. Interfering with the expression and/or the function of SR might be one way to limit the impact of DEP on lung immune response.

No MeSH data available.


Related in: MedlinePlus