title: Effects of acetaldehyde on human airway constriction and inflammation.
abstract: The purpose of the present study was to determine the effects of acetaldehyde on airway smooth muscle constriction and inflammation. An oral ethanol provocation test was performed in Japanese asthmatics to measure pulmonary function, blood ethanol, acetaldehyde and histamine. Acetaldehyde dehydrogenase 2 (ALDH2) genotype was determined by polymerase chain reaction (PCR) and ethanol patch test. Human bronchi and mast cells were stimulated with acetaldehyde in vitro. Mite allergen-sensitized mice were inoculated with intranasal acetaldehyde. Approximately half the asthmatic subjects developed bronchoconstriction with concomitant increases in blood acetaldehyde and histamine, which was associated with genetically reducedALDH2 activities. In vitro acetaldehyde stimulation induces bronchoconstriction and degranulation of human mast cells. It also induced granulocyte macrophage colony stimulating factor (GM-CSF) production and nuclear factor (NF)-kappaB activation in human bronchi and increased mite allergen-sensitized allergic inflammation in a murine model of asthma. We conclude that acetaldehyde has potential effects on human airway by two distinct mechanisms. As a metabolite of alcohol, its elevation following alcohol consumption induces airway mast cells to release histamine, which results in exacerbation of asthma in susceptible populations. And as an air pollutant contained in cigarette smoke, for example, its inhalation potentially increases airway inflammation.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsuse
authors.forename: Chizu
authors.initials: C
authors.lastname: Fukushima
authors.forename: Terufumi
authors.initials: T
authors.lastname: Shimoda
authors.forename: Asai
authors.initials: A
authors.lastname: Sadahiro
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000079:Acetaldehyde / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D000284:Administration, Oral; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D016084:Bronchoconstriction / Q000187:drug effects*; D000431:Ethanol / Q000097:blood* / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006632:Histamine / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: D016328:NF-kappa B; D000431:Ethanol; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde