[Cellular pathophysiologic effects of various air pollutants on the airways]

Both epidemiological and experimental data indicate that major health consequences of urban air pollution i.e., respiratory symptoms are related, at least in part, to an alteration in the cellular processes implicated in bronchial responsiveness. In the Laboratory, we have set up techniques which enable to pre-expose in vitro human isolated bronchi to some air pollutants. Using these techniques, we have examined the dosimetric relationships and the cellular mechanisms of bronchial responsiveness altered by nitrogen dioxide (NO2), ozone (O3) or aldehydes such as acrolein. The combined effects of gas pollutants and passive immunological sensitization on bronchial hyperresponsiveness have also been studied. As a general rule, experimental protocols consisted in a comparison of the responsiveness of human bronchial tissues (obtained at thoracotomy from patients undergoing resection for pulmonary carcinoma) following ex vivo exposure to air pollutants with that of paired tissues unexposed to pollutants which acted as temporal controls. We have observed that the responsiveness of human isolated bronchi is increased following pre-exposure to NO2 or O3 or to acrolein for 15 to 30 min, at concentrations in the range of ppm and microM, respectively. A common target for the action of these pollutants on airway smooth muscle reactivity has been identified i.e., the release of intracellular stored calcium ions. Direct measurements of cytosolic calcium concentration in isolated airway smooth muscle cells exposed to pollutants have confirmed this hypothesis. Finally, we have obtained results indicating that passive sensitization and exposure to pollutants act in a additional manner on human bronchial smooth muscle reactivity in response to both specific antigen and non specific agonists. Collectively, these experimental in vitro results enable (i) to establish dosimetric relationships, (ii) to examine the cellular mechanisms and (iii) to identify populations at risk for various gas pollutants.