The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in human subjects.
BACKGROUND
The glutathione-S-transferase Mu 1 (GSTM1) null genotype has been reported to be a risk factor for acute respiratory disease associated with increases in ambient air ozone levels. Ozone is known to cause an immediate decrease in lung function and increased airway inflammation. However, it is not known whether GSTM1 modulates these ozone responses in vivo in human subjects.


OBJECTIVE
The purpose of this study was to determine whether the GSTM1 null genotype modulates ozone responses in human subjects.


METHODS
Thirty-five healthy volunteers were genotyped for the GSTM1 null mutation and underwent a standard ozone exposure protocol to determine whether lung function and inflammatory responses to ozone were different between the 19 GSTM1 wild type and 16 GSTM1 null volunteers.


RESULTS
GSTM1 did not modulate lung function responses to acute ozone. Granulocyte influx 4 hours after challenge was similar between GSTM1 normal and null volunteers. However, GSTM1 null volunteers had significantly increased airway neutrophils 24 hours after challenge, as well as increased expression of HLA-DR on airway macrophages and dendritic cells.


CONCLUSIONS
The GSTM1 null genotype is associated with increased airways inflammation 24 hours after ozone exposure, which is consistent with the lag time observed between increased ambient air ozone exposure and exacerbations of lung disease.
Alexis
Neil E
NE
Center for Environmental Medicine, Asthma and Lung Biology, UNC School of Medicine, Chapel Hill, NC 27599-7310, USA.
Zhou
Haibo
H
Lay
John C
JC
Harris
Bradford
B
Hernandez
Michelle L
ML
Lu
Tsui-Shan
TS
Bromberg
Philip A
PA
Diaz-Sanchez
David
D
Devlin
Robert B
RB
Kleeberger
Steven R
SR
Peden
David B
DB
D000328:Adult; D016207:Cytokines / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006684:HLA-DR Antigens / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics*; D013183:Sputum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D005982:Glutathione Transferase; D006684:HLA-DR Antigens; D010126:Ozone