Am. J. Respir. Cell Mol. Biol., Volume 23, Number 2, August, 2000 247-254

Synergistic Effect of Diesel Organic Extracts and Allergen Der p 1 on the Release of Chemokines by Peripheral Blood Mononuclear Cells from Allergic Subjects
Involvement of the MAP Kinase Pathway

Olivier Fahy, Hamida Hammad, Stéphanie Sénéchal, Joël Pestel, André-Bernard Tonnel, Benoît Wallaert, and Anne Tsicopoulos

INSERM U416, Institut Pasteur de Lille, and Hôpital Calmette, Centre Hospitalier Régional et Universitaire de Lille, Lille, France

The organic compounds of diesel exhaust particles (DEP-PAHs) have been shown to favor immunoglobulin production and bronchial hyperresponsiveness and to affect cytokine and chemokine productions. To evaluate if diesel exhaust could act in synergy with a house dust mite allergen (Der p 1), peripheral blood mononuclear cells from allergic patients were exposed to DEP-PAHs, with or without purified Der p 1. DEP-PAHs and Der p 1 separately induced an increase in interleukin (IL)-8, regulated on activation, normal T cells expressed and secreted (RANTES), and tumor necrosis factor- concentrations. Interestingly, a synergy between the two stimuli was also observed. In the case of monocyte chemotactic protein (MCP)-1, DEP-PAHs reduced the release, whereas Der p 1 enhanced it. A simultaneous exposure led to reduced production as compared with allergen exposure alone, but still represented an increase as compared with the control exposure. Mitogen-activated protein (MAP) kinase Erk1/2 antagonist mainly inhibited the release of MCP-1, whereas MAP kinase p38 antagonist mainly suppressed the release of IL-8 and RANTES. Messenger RNA expression correlated with protein measurements. Moreover, supernatants from cells exposed to both DEP-PAHs and Der p 1 had a significant chemotactic activity on neutrophils and eosinophils. These findings suggest that simultaneous exposure of allergic patients to DEPs and allergens could result in high local chemokine levels via MAP kinase pathways activation, increasing the likelihood of reaching a critical threshold leading to the initiation of respiratory allergic symptoms.

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