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The glutathione-S-transferase mu 1 (GSTM1) null genotype and increased neutrophil response to low-level ozone (0.06 ppm).
Alexis, N., J. Lay, H. Zhou, C. Kim, M. Hernandez, H. Kehrl, M. Hazucha, R. Devlin, D. Diaz-Sanchez, AND D. Peden. The glutathione-S-transferase mu 1 (GSTM1) null genotype and increased neutrophil response to low-level ozone (0.06 ppm). JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. Journal of Allergy Clinical Immunology, 131(2):610-02, (2013).
THIS MANUSCRIPT WAS ORGINALLY CLEARED VIA A PAPER FILE EPHD-12-045 AND ENTERED IN THE SCIENCE INVENTORY
Background: Exposure of healthy young adults to 03 modulates immune cell biology in the airways and causes a significant increase in neutrophilic inflammation which can vary considerably in magnitude across individuals. The GSTM1null genotype modulates Oj-induced inflammation, but it is unknown whether it is associated with the neutrophil (PMN) response phenotype. Objectives: To determine if neutrophil (PMN) responsiveness and GSTM1 status affect changes in immune cell biology in the airways following low level 03 exposure. Methods: 24 healthy young adults (20-33 yr) underwent a controlled chamber exposure to clean air (CA) and 0.06 ppm 0 3 for 6.6 hours. Cell surface phenotypes, phagocyte function, cell counts and cytokines were assessed in sputum 16-18 hours post exposure. PMN response was defined as %PMN post 03 -%PMN post CA and a PMN response cut-off level of 12 distinguished neutrophil Responders (>12 N=13) and Non-Responders «12 N=ll). Results: The mean (±SEM) PMN response was significantly elevated in Responders versus Non-Responders [%PMN 27 (3) vs %PMN 3 (2), p<0.05]. Responders showed significant (p<0.05) 03 responses with elevated expression of CD l lb, CD14, CD16, CD86, HLA-DR, and CD54, and decreased phagocytosis versus Non-Responders. Responders had significantly (p<0.05) elevated IL-8, IL-6, TNFa at baseline suggesting a primed inflammatory phenotype. The GSTM1null genotype was significantly associated with the Responder group (odds ratio = 13, p<0.05). Conclusions: A PMN response phenotype to low dose (0.06 ppm) 03 is present in healthy individuals. Baseline inflammation and the GSTM1null genotype are associated risk factors for altered immune cell function following 0.06 ppm 0 3.