title: Isocyanate-conjugated human lung epithelial cell proteins: A link between exposure and asthma?
abstract: BACKGROUND
  Isocyanates are a group of highly reactive cross-linking chemicals that cause airway inflammation and asthma in exposed individuals. Isocyanates have been detected along the airway epithelia of exposed workers and animals, prompting the hypothesis that isocyanates can directly bind to epithelial cell proteins.
  
  
  OBJECTIVE
  We tested the hypothesis that hexamethylene diisocyanate (HDI) binds directly to lung epithelial cell proteins and initiated studies to evaluate the immunostimulatory potential of HDI-conjugated lung epithelial cell proteins.
  
  
  METHODS
  Human lung epithelial cell lines were exposed to vapor- and liquid-phase HDI, and the cellular proteins were analyzed for HDI conjugation by Western blotting and tested for the ability to induce lymphocyte proliferation in vitro.
  
  
  RESULTS
  A number of epithelial cell polypeptides, ranging from 25 to 110 kd in apparent molecular weight, were conjugated with HDI after exposure of the human lung epithelial cell lines (A549 and NCI-H292) to HDI concentrations greater than 0.005% (vol/vol) in the liquid phase. Vapor-phase HDI exposure resulted in a more restricted HDI conjugation pattern, with major HDI-conjugated polypeptides migrating at 47, 71, and 91 kd. HDI-conjugated epithelial cell proteins specifically stimulated proliferation of PBMCs from subjects with isocyanate-induced asthma but not HDI-exposed nonasthmatic individuals or atopic subjects with nonisocyanate-related asthma.
  
  
  CONCLUSIONS
  The data demonstrate that epithelial cell proteins readily react with HDI and that HDI-conjugated epithelial cell proteins can stimulate lymphocyte proliferation. Further characterization and evaluation of HDI-conjugated epithelial cell proteins will elucidate their potential role in the pathogenesis of isocyanate-induced asthma.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Wisnewski
authors.forename: R
authors.initials: R
authors.lastname: Lemus
authors.forename: M H
authors.initials: MH
authors.lastname: Karol
authors.forename: C A
authors.initials: CA
authors.lastname: Redlich
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000918:Antibody Specificity; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000209:etiology; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003485:Cyanates / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism*; D004781:Environmental Exposure / Q000009:adverse effects; D004847:Epithelial Cells / Q000737:chemistry*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D017953:Isocyanates; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008168:Lung / Q000166:cytology*
chemical_list: D000393:Air Pollutants; D002352:Carrier Proteins; D003485:Cyanates; D007106:Immune Sera; D017953:Isocyanates; C015262:1,6-hexamethylene diisocyanate