Asbestos exposure increases paracellular transport of fibrin degradation products across human airway epithelium.
The inflammatory response to asbestos fiber inhalation suggests that the distal respiratory epithelium is an important early target of asbestos-induced injury. We have previously found that asbestos exposure increases the fibrinolytic activity and mannitol permeability of human airway epithelial cell monolayers. Because fibrin degradation products (FDP) are potent inflammatory mediators, we asked whether asbestos fiber exposure would increase the transepithelial flux of FDP into the interstitial space. To stimulate the pericellular environment following fiber deposition, asbestos-exposed epithelial monolayers grown on permeable filters were covered with human plasma containing fluorescein isothiocyanate (FITC)-labeled human fibrinogen. After 24 h, nearly twice as much FITC-FDP appeared in the abluminal chamber of asbestos-exposed monolayers compared with unexposed controls. This did not result solely from increased degradation product production because asbestos-exposed epithelium was more permeable at all apical FDP concentrations. The proteins that crossed asbestos-exposed monolayers included biologically relevant high-molecular-weight FDP, as demonstrated by streptavidin blotting of biotin-labeled FDP. We also found that FDP flux was not vectorial, was not saturable, did not involve proteolytic processing of FDP, and did not require active transport. Thus asbestos exposure increases the paracellular flux of intact FDP across human airway epithelium. This represents a novel mechanism whereby fiber-induced epithelial dysfunction may initiate and sustain inflammation in the distal airspace.
Gross
T J
TJ
Department of Internal Medicine, College of Medicine, University of Iowa Hospitals and Clinics, Iowa City 52242.
Cobb
S M
SM
Peterson
M W
MW
D001194:Asbestos / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001777:Blood Coagulation / Q000502:physiology; D001980:Bronchi / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D004553:Electric Conductivity; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008970:Molecular Weight; D010539:Permeability
D005338:Fibrin Fibrinogen Degradation Products; D001194:Asbestos