Published ahead of print on October 5, 2006, doi:10.1164/rccm.200509-1424OC Am. J. Respir. Crit. Care Med., Volume 174, Number 12, December 2006, 1335-1341 A more recent version of this article appeared on December 15, 2006
Submitted on September 12, 2005 Glutathione-S-Transferase M1 and P1 Prevent Aggravation of Allergic Responses by Secondhand SmokeFrank D Gilliland1*,1 Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA, 2 Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA; Institute of Environmental Health, China Medical University, Taichung, Taiwan, 3 Division of Clinical Immunology, Department of Medicine, David Geffen School of Medicine at UCLA, The Hart and Louis Laboratory, Los Angeles, CA, USA * To whom correspondence should be addressed. E-mail: gillilan{at}usc.edu.
Rationale. Secondhand tobacco smoke (SHS) and traffic- related air pollutants are associated with asthma and allergy. Diesel exhaust particles (DEP) and SHS can interact with allergens in exacerbating allergic airway diseases through generation of reactive oxygen species. Glutathione-S-Transferases metabolize reactive oxygen species and detoxify electrophilic xenobiotics present in SHS and DEP. Objectives. We tested the hypotheses that functional Glutathione-S-Transferase M1 (GSTM1) null genotype and P1 (GSTP1) codon 105 variants (Ile105 and Val105) are determinants of allergic responses SHS and that responses to SHS and DEP are correlated. Methods and Measurements. In a randomized placebo-controlled crossover trial, 19 ragweed allergen-sensitive subjects who had previously participated in a DEP trial were challenged intranasally with allergen after having been exposed to either clean air or SHS at separate visits. Nasal allergen-specific immunoglobulin E, histamine, interleukin-4, and interferon- Key words: GSTM1, GSTP1, IgE, Histamine, tobacco smoke
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levels were measured before and after allergen challenge. Main Results. Individuals with GSTM1 null or GSTP1 Ile105 genotypes showed larger nasal responses to allergens with SHS compared with clean air. GSTM1 null subjects had a larger increase in immunoglobulin E (IgE) than GSTM1 present subjects (173.3 median versus 46.7 U/mL, p=0.03) and the Ile105 GSTP1 genotype subjects had increased histamine (median 10.2 versus 4.6 nM, p=0.01) following SHS plus allergen challenge. Responses to SHS and DEP were correlated. Enhancement of IgE and histamine was largest in the subjects with both the GSTM1 null and GSTP1 Ile/Ile genotypes. Conclusions. GSTM1 and GSTP1 are important cytoprotective factors that reduce SHS and DEP exacerbation of allergic responses.
