Effects of diesel organic extracts on chemokine production by peripheral blood mononuclear cells,☆☆,

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Abstract

Background: Polyaromatic hydrocarbons (PAHs) associated with diesel exhaust particles (DEPs) are found in the atmospheric urban pollution. Such compounds have been shown to favor IgE production, bronchial hyperresponsiveness, and airway inflammation. Chemokines are a group of chemotactic cytokines involved in the recruitment of inflammatory cells. Objective: We investigated the effect of DEP-PAHs on the release and mRNA expression of IL-8, MCP-1, and RANTES by PBMCs obtained from healthy subjects. Methods: Protein production in supernatants was assessed by ELISA, and mRNA expression was evaluated by semiquantitative RT-PCR. Results: Secretion of IL-8 and RANTES increased in a dose-dependent manner with increasing concentrations of DEP-PAHs (range, 0.5 ng to 50 ng/mL). On the contrary, the release of MCP-1 was significantly inhibited, also in a dose-dependent manner. Messenger RNA production coding for IL-8, RANTES, and MCP-1 showed parallel variations to the production of the correspondent proteins. Effects of DEP-PAHs became significant at 7 hours and up to 48 hours time culture for MCP-1, and up to 24 hours time culture for IL-8 and RANTES. Moreover, supernatants from DEP-PAH–activated cells, compared with those of controls, exhibited a significantly enhanced chemotactic activity for neutrophils and eosinophils, which was significantly inhibited by pretreatment with anti-IL-8 and anti-RANTES neutralizing antibodies, respectively. Conclusion: These findings suggest that the chemokine pathways are modulated by DEP-PAHs at the transcriptional level, reinforcing the idea that the development of inflammatory reactions might be affected by diesel exhaust emission. (J Allergy Clin Immunol 1999;103:1115-24.)

Section snippets

Generation of diesel exhaust

DEPs were obtained from a light-duty diesel-powered passenger car (Renault, pollution department, Boulogne Billancourt) used under the standard European Community cycle, representing the typical conditions encountered while driving in an urban setting and during short trips in a nonurban setting. DEPs were impacted on a Pallflex filter in a cyclone equipped with a dilution tunnel. After 3 cycles, the filter was removed from the tunnel and immediately used for organic extraction of the DEP-PAHs.

Extraction of DEP-PAHs

PBMC viability

The viability of PBMCs cultured in complete RPMI medium and incubated with various concentrations of DEP-PAHs, CH2 Cl2 , or medium alone during 7 to 48 hours time culture was first examined. The volume of CH2 Cl2 or DEP-PAHs solubilized in dichloromethane added to 1 mL medium was limited to 2 μL. The toxic effect on PBMCs was found to be nonexistent over 24-hour culture (viability >97% for all conditions) and remained very low even after 48 hours (viability for CH2 Cl2 : 95.3 ± 1.7%; 5 ng

DISCUSSION

DEPs and associated DEP-PAHs have been shown in several studies to have a broad spectrum of action in many aspects of the inflammatory reaction. In this context, we sought to investigate whether DEP-PAHs could also affect the production of chemokines.

This study demonstrates that the organic extract of diesel exhaust particles can modulate the release of chemokines produced by mononuclear cells of normal donors. This effect was shown to be dose-dependent and to take place early, already a couple

Acknowledgements

We are grateful to Philippe Gosset, Philippe Lassalle, and Michel Joseph for critical review of this work. We thank Pascal Dorlhène, Gilles Jouvenot, and Michèle Chevrier from the staff of Renault Lardy for providing the DEP-PAHs and for the HPLC analysis.

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    Supported by a grant from ADEME and Institut Pasteur de Lille and by PRIMEQUAL-PREDIT grant No. 97034 from Ministère de l’Environnement.

    ☆☆

    Reprint requests: A. B. Tonnel, MD, INSERM U-416, Institut Pasteur de Lille, 1 rue du Pr Calmette, BP 245, 59 019 LILLE, France.

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