Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system

doi:10.1016/S0091-6749(98)70269-6

Journal of Allergy and Clinical Immunology

Volume 102, Issue 4, October 1998, Pages 539-554

https://doi.org/10.1016/S0091-6749(98)70269-6 Get rights and content

Abstract

There is growing evidence that fossil fuel combustion products act as adjuvants in the immune system and may lead to enhancement of allergic inflammation. Through this mechanism, particulate air pollutants may be an important contributor to the increased prevalence and morbidity of asthma and allergic rhinitis. In this communication we focus on the role of diesel exhaust particles (DEPs) in skewing the immune response towards IgE production and induction of allergic inflammation. We review experimental studies in animals and humans showing that DEPs enhance IgE production by a variety of mechanisms, including effects on cytokine and chemokine production, as well as activation of macrophages and other mucosal cell types. We discuss metabolic and cellular activation pathways linked to chemicals such as polycyclic aromatic hydrocarbons contained in DEPs and demonstrate how these molecular events may impact cytokine, chemokine, and accessory molecule expression in the immune system. (J Allergy Clin Immunol 1998;102:539-54.)

Section snippets

CELLULAR AND CYTOKINE ELEMENTS INVOLVED IN IgE PRODUCTION

IgE plays a major role in the pathogenesis of allergic inflammation in humans, both in the early and late phase of the mucosal response to allergens.¹⁹ Stratification of total IgE serum levels in a population acts as a good predictor for the prevalence of asthma in the identified subgroup populations.²⁰ Before discussing the effects of DEPs on IgE synthesis, it is appropriate to briefly review some basic processes in IgE production.²¹ Although IgE production entails B-cell Ig isotype switching

ANIMAL STUDIES INDICATING THAT THE DEP IS AN ADJUVANT FOR IgE PRODUCTION

Animal studies have provided definitive data that DEPs, or extracts made from DEPs, affect IgE production (Table II).26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39

. Adjuvant effect of DEPs on in vivo allergic responses in animals

Effect or response	References
Increased total IgE production	27
Allergen-specific IgE enhancement after intra-peritoneal, intranasal, intratracheal, inhalational, or foot pad challenge with particles mixed with allergen	28-32
Intraperitoneal pyrene, extracted from DEP,

HUMAN STUDIES INDICATING THAT THE DEP IS AN ADJUVANT FOR IgE PRODUCTION

Human studies have extended the findings obtained in animal models (Table III).

. Adjuvant effects of DEPs on in vivo allergic responses in humans

Effects	References
Effects of aerosolized DEPs on nasal allergic response
• Increased local production of IgE and IgE-secreting cells	40
• Qualitatively different IgE isoforms produced through alternative splicing of ϵ mRNA	40, 42
• Augmented production of allergen-induced antigen-specific IgE	44
• Nonspecific stimulation of a broad cytokine profile in the

DEP EFFECTS ON CELLULAR IMMUNE ELEMENTS INVOLVED IN ALLERGIC INFLAMMATION

Fig 2 outlines some of the cells involved in IgE production, including B lymphocytes, T lymphocytes, and APCs and also demonstrates how DEPs may interact with these elements. We have previously discussed the finding that intranasal challenge with DEPs selectively enhances the number of IgE-secreting B lymphocytes in the nasal mucosa.⁴⁰ Additionally, DEP extracts have been shown to enhance IgE production in normal human tonsillar and peripheral blood B lymphocytes,⁴³ as well as in a human

FUNCTIONAL CONSEQUENCES OF DEP-INDUCED MACROPHAGE MODULATION AND ITS RELEVANCE TO ALLERGIC INFLAMMATION

One potential mechanism for the adjuvant effect of DEPs on allergic inflammation is the enhancement of the role of macrophages as APCs. Because APCs interact with T cells, a perturbation of those cellular interactions may effect cytokine production in T cells (Fig 2). In this regard, PAHs have been demonstrated to enhance major histocompatibility type-II gene expression in murine macrophages, but this work needs to be confirmed.⁶³ In our own studies we have focused on CD80 protein and message

DEP EFFECTS ON OTHER MUCOSAL CELL TYPES

In addition to the effects on cells of the immune system, DEPs also influence other mucosal cell types that play a role in allergic inflammation. Terada et al⁷³ found that DEP extracts enhance human eosinophil adhesion to nasal epithelial cells, as well as causing eosinophil degranulation. Because eosinophil degranulation is associated with the release of mediators that promote allergic inflammation, this suggests that DEPs can promote eosinophil-mediated hypersensitivity. In earlier work the

METABOLIC PATHWAYS USED BY PAH TO ACTIVATE MACROPHAGES AND POSSIBLY OTHER CELL TYPES IN THE MUCOSAL IMMUNE SYSTEM

Although metabolic pathways for PAHs are well described in hepatocytes, comparatively little is known about these pathways in the cells of the immune system (Fig 6).76, 77

. Schematic showing major metabolic pathways for DEP-derived PAHs and their quinone conversion products in mammalian cells. Notice that the 2 major metabolic pathways operate by means of distinct genetic response elements, which induce promoters of phase I and phase II drug metabolizing enzymes, respectively.

The best

METABOLIC CONVERSION OF PAH AND QUINONES INDUCE ROS, LEADING TO ACTIVATION OF INTRACELLULAR SIGNALING PATHWAYS AND INDUCTION OF GENE TRANSCRIPTION

The CYP1A1 catalytic cycle involves substrate binding followed by binding and activation of molecular oxygen to reactive intermediate species, which hydroxylate the substrate.¹⁰⁴ The formation of hydrogen peroxide (H₂ O₂ ) and water as end products of the catalytic process is postulated to result from autoxidation of the cytochrome P450 complex.¹⁰⁴ The initial reactive oxygen species that are generated are superoxide anions; spontaneous dismutation of superoxide anion yields H₂ O₂ . One

CONCLUSION

The industrial revolution began about 2 centuries ago, and the diesel engine went into production a little less than a century ago. Particulates generated by related human activities have now reached a level where they may reflect enough sunlight to lower global temperatures. Studies reviewed in this article show our new and increasing understanding of such materials, particularly DEPs and the chemicals contained therein. These data indicate that DEPs can act as mucosal adjuvants at the

Acknowledgements

We thank Peggy Shih for skillful preparation of the manuscript and Lynne Olson for designing and drawing the front cover illustration.

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^☆: From the Division of Clinical Immunology/Allergy, Department of Medicine, UCLA School of Medicine, University of California, Los Angeles.

^☆☆: Supported by a United States Public Health service grant, AI-34567 (UCLA Asthma, Allergy, and Immunologic Disease Center) to Andre E. Nel and Andrew Saxon and funded by the National Institute of Allergy and Infectious Disease and the National Institutes of Environmental Health Sciences.

^★: Reprint requests: Andre Nel, MD, Division of Clinical Immunology/Allergy, Department of Medicine, UCLA Medical School, 10833 Le Conte Ave, Los Angeles, CA 90095-1680.

^★★: 0091-6749/98 $5.00 + 0 1/1/92841

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Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system☆,☆☆,★,★★

Abstract

Section snippets

CELLULAR AND CYTOKINE ELEMENTS INVOLVED IN IgE PRODUCTION

ANIMAL STUDIES INDICATING THAT THE DEP IS AN ADJUVANT FOR IgE PRODUCTION

HUMAN STUDIES INDICATING THAT THE DEP IS AN ADJUVANT FOR IgE PRODUCTION

DEP EFFECTS ON CELLULAR IMMUNE ELEMENTS INVOLVED IN ALLERGIC INFLAMMATION

FUNCTIONAL CONSEQUENCES OF DEP-INDUCED MACROPHAGE MODULATION AND ITS RELEVANCE TO ALLERGIC INFLAMMATION

DEP EFFECTS ON OTHER MUCOSAL CELL TYPES

METABOLIC PATHWAYS USED BY PAH TO ACTIVATE MACROPHAGES AND POSSIBLY OTHER CELL TYPES IN THE MUCOSAL IMMUNE SYSTEM

METABOLIC CONVERSION OF PAH AND QUINONES INDUCE ROS, LEADING TO ACTIVATION OF INTRACELLULAR SIGNALING PATHWAYS AND INDUCTION OF GENE TRANSCRIPTION

CONCLUSION

Acknowledgements

J Allergy Clin Immunol

Toxicology

Toxicology

Toxicology

Fundam Appl Toxicol

Fundam Appl Toxicol

Free Radic Biol Med

Toxicology

J Allergy Clin Immunol

J Allergy Clin Immunol

J Aerosol Sci

Toxicol Appl Pharmacol

Cancer Lett

J Allergy Clin Immunol

J Biol Chem

J Biol Chem

J Biol Chem

Toxicol Appl Pharmacol

Biochem Biophys Res Commun

Toxicol Appl Pharmacol

Toxicology

J Biol Chem

Biochem Pharmacol

A case of a periodical affection of the eyes and chest

Medico-Chirurgical Trans

On the catarrhus aestivus or summer catarrh

London: Medico-Chirurgical Trans

Catarrhus Aestivus. Causes and nature

Hay fever, hay asthma—its causes, diagnosis and treatments

Prevalence of asthma and hay fever in England and Wales

Br Med J

Asthma and allergic rhinitis in Swedish conscripts

Clin Exp Allergy

Studies of prevalence of Japanese cedar pollinosis among residents in a densely cultivated area

Ann Allergy

Asthma death in England and Wales 1931-1985: evidence for true increase in asthma mortality

J Epidemiol Community Health

Guidelines for the diagnosis and management of asthma. National Heart, Lung, and Blood Institute—National Asthma Education Program

Pediatr Asthma Allergy Immunol

Changes in asthma prevalence: two surveys 15 years apart

Arch Dis Child

Prevalence of asthma in Finnish young men

Br Med J

A community based study of the epidemiology of asthma

Am Rev Respir Dis

Symptoms of bronchial hyperreactivity and asthma in relation to environment factors

Arch Dis Child

Prevalence of atopy and range of bronchial response to methacholine in 7 and 11 year old schoolchildren

Arch Dis Child

Effects of inhalable particles on respiratory health of children

Am Rev Respir Dis

Human health effects of air pollution

Environ Health Perspect

Global increases in allergic respiratory disease: the possible role of diesel exhaust particles

Ann Allergy Asthma Immunol

Human cell mutagenicity of polycyclic aromatic hydrocarbon components of diesel emissions

Dev Toxicol Environ Sci

Late-phase IgE-mediated reactions

J Clin Immunol

Association of asthma with serum IgE levels and skin-test reactivity to allergens

N Engl J Med

Chemokines active on eosinophils: potential roles in allergic inflammation

J Exp Med

How T cells direct IgE switching

CD40 stimulation provides an IFN-gamma-independent and Th-4-dependent differentiation signal directly to human B-cells for IgE production

J Immunol

Normal bronchial epithelial cells constitutively produce the anti-inflammatory cytokine interleukin-10, which is downregualted in cystic fibrosis