Effect of diesel exhaust particles on allergic reactions and airway responsiveness in ovalbumin-sensitized brown Norway rats

Abstract

Diesel exhaust particles (DEP) are the major constituent of ambient particulate matter in urban environments and occupational settings. Exposure to DEP in combination with an allergen has been demonstrated to enhance allergen-related airway inflammation, immunoglobulin (Ig) E production, and airway responsiveness (AR) in human and in animal models. However, the mechanisms behind these effects of DEP are not yet fully understood. In this study, we compared the effects of short-term DEP exposure on ovalbumin (OVA)-mediated airway responses under two exposure protocols using an OVA-allergic rat model. Male Brown Norway rats were sensitized to aerosolized OVA (40.5 ± 6.3 mg/m 3) on days 1, 8, and 15, and challenged with OVA on day 29. The rats were exposed to DEP (20 mg/m 3) for 4 h/day for 5 consecutive days either before sensitization (protocol A) or before OVA challenge on days 24-28 (protocol B). Control animals received filtered air and aerosolized saline instead of DEP and OVA, respectively. The results showed that DEP exposure 1) elicited an adjuvant effect on OVA-specific IgE and IgG production in serum under both protocols; 2) significantly reduced OVA-induced airway inflammation and lung injury in protocol A, but increased these markers in protocol B; 3) markedly lowered OVA-induced production of nitric oxide, reactive oxygen species, and interleukin (IL)-10 and IL-12 by alveolar macrophages (AM) in protocol A, but increased these parameters in protocol B; 4) significantly lowered the numbers of T cells and their CD4 + and CD8 + subsets in lungdraining lymph nodes in protocol A, but increased these cell counts in protocol B; 5) reduced intracellular glutathione in AM and lymphocytes in both protocols; and 6) enhanced AR of the OVA-sensitized rats to methacholine challenge in protocol B. These results suggest that the effects of DEP on the immune system, including aggravation or exacerbation of asthma, may be greatly influenced by allergic immune status and time of antigen exposure. vi

Enhanced nitric oxide and reactive oxygen species production and damage after inhalation of silica

“…In our current study, we determined that NO and ROS production continue after cessation of silica exposure and thus may, in part, be responsible for disease progression. Furthermore, particulate silica was determined to be highly associated with iNOS in AMs, unlike other particles, such as carbon black (Millecchia, unpublished data) and diesel exhaust particles (Dong et al, 2005), which are not associated with increased iNOS in AMs. Whether the iNOS upregulation is a direct result of silica phagocytosis, or whether other signals are triggering iNOS increases remains to be determined.…”

Prolonged occupational exposure leads to allergic airway sensitization and chronic airway and systemic inflammation in professional firefighters

“…Several studies have shown that persistent exposure to particulate air pollution poses a significant factor responsible for the observed increased prevalence of atopy [6e8,41e44]. Experimental studies examining the challenge with diesel exhaust particles in combination with allergens have shown a significantly higher allergen specific IgE induction compared to the challenge with the allergen alone [44]. Dong et al [44] demonstrated that exposure to diesel exhaust particles prior to ovalbumin sensitization in rats exacerbates the allergic responses to the subsequent challenge with OVA in OVA-sensitized rats.…”

“…Experimental studies examining the challenge with diesel exhaust particles in combination with allergens have shown a significantly higher allergen specific IgE induction compared to the challenge with the allergen alone [44]. Dong et al [44] demonstrated that exposure to diesel exhaust particles prior to ovalbumin sensitization in rats exacerbates the allergic responses to the subsequent challenge with OVA in OVA-sensitized rats. Moreover, studies in people living in areas with high traffic have shown increased sensitization to outdoor allergens [45,46].…”

Diesel Exhaust Particle Exposure Reduces Expression of the Epithelial Tight Junction Protein Tricellulin

“…Diesel exhaust particles (DEP), which result from the incomplete combustion of diesel fuel, are a major component of airborne PM and have been largely studied for their role in enhancing immune responses in allergic diseases such as asthma. While multiple studies have documented the ability of inhaled DEP to impact and activate cells of the immune system [8][9][10], less is known about the effect of DEP on airway epithelial cells.…”