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Toxicologic Pathology
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Articles

Effects of Residual Oil Fly Ash (ROFA) in Mice with Chronic Allergic Pulmonary Inflammation

Fernanda M. Arantes-Costa1, Fernanda D.T.Q.S. Lopes1, Alessandra C. Toledo1, Pedro A. Magliarelli-Filho1, Henrique T. Moriya3, Regiane Carvalho-Oliveira2, Thais Mauad2, Paulo H. N. Saldiva2 and Milton A. Martins1

1 Department of Medicine, School of Medicine, University of São Paulo, Brazil
2 Department of Pathology, School of Medicine, University of São Paulo, Brazil
3 Escola Politecnica, University of São Paulo, Brazil

Correspondence: Mílton A. Martins, M.D., Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, Sala 1216, 01246-903 São Paulo SP, Brazil; E-mail:mmartins{at}usp.br

Exposure to particulate matter (PM) air pollution is associated with increased asthma morbidity. Residual oil flash ash (ROFA) is rich in water-soluble transition metals, which are involved in the pathological effects of PM. The objective of this study was to investigate the effects of intranasal administration of ROFA on pulmonary inflammation, pulmonary responsiveness, and excess mucus production in a mouse model of chronic pulmonary allergic inflammation. BALB/c mice received intraperitoneal injections of ovalbumin (OVA) solution (days 1 and 14). OVA challenges were performed on days 22, 24, 26, and 28. After the challenge, mice were intranasally instilled with ROFA. After forty-eight hours, pulmonary responsiveness was performed. Mice were sacrificed, and lungs were removed for morphometric analysis. OVA-exposed mice presented eosinophilia in the bronchovascular space (p < .001), increased pulmonary responsiveness (p < .001), and epithelial remodeling (p = .003). ROFA instillation increased pulmonary responsiveness (p = .004) and decreased the area of ciliated cells in the airway epithelium (p = .006). The combined ROFA instillation and OVA exposure induced a further increase in values of pulmonary responsiveness (p = .043) and a decrease in the number of ciliated cells in the airway epithelium (p = .017). PM exposure results in pulmonary effects that are more intense in mice with chronic allergic pulmonary inflammation.

Key Words: asthma • experimental asthma models • ROFA • particulate matter • epithelial remodeling • eosinophils • pulmonary responsiveness

Abbreviations: BAL, bronchial alveolar lavage • CEMIB, Multidisciplinary Center for Biological Investigation, State University of Campinas • HE, hematoxylin-eosin • IgE, immunoglobulin E • IgG, immunoglobulin G • IL, interleukin • Mch, methacholine • NIH, National Institutes of Health • OVA, ovalbumin • PAS-AB, periodic acid-Schiff and alcian blue • PM, particulate matter • ROFA, residual oil fly ash • SEM, standard error mean • TNF{alpha}, tumoral necrosis factor {alpha}

This version was published on July 1, 2008

Toxicologic Pathology, Vol. 36, No. 5, 680-686 (2008)
DOI: 10.1177/0192623308317427
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