IV. ISAM JOINT MEETING Aerosols – Good and Bad Fate of inhaled particles after interaction with the lung surface Peter Gehr * , Fabian Blank and Barbara M. Rothen-Rutishauser Institute of Anatomy, Division of Histology, University of Bern, Baltzerstr. 2, CH-3000, Bern 9, Switzerland \ INTRODUCTION Epidemiological studies give evidence that the inhalation of fine particles (0.1–2.5 mm) and nanoparticles (0.1 mm) may cause increased pulmonary and cardio- vascular morbidity and mortality. 1,2 Nanoparticles are reported to be particularly toxic. 3 A huge internal surface area of 140 m 2,4 is available for interaction with inhaled particles. Once deposited, particles are displaced by sur- face forces of the surfactant film at the air-liquid inter- face. 5,6 This gets them into close association with epithelial cells and cells of the defense system, airway or alveolar macrophages (AM) and dendritic cells (DC). Little is known about the interaction of such particles with lung cells, how they may cross the epithelial barrier and how they may penetrate the capillaries in the pulmonary tissue. The wall structures of the airways and alveoli act as a series of structural and functional barriers which pro- tects the respiratory system against harmful and innoc- uous particles. 7 It was the aim of this study to find out how immunocompetent DC 8,9 located in or at the base of the airway epithelium take up inhaled particulate antigens and how AM on top of the epithelium may collaborate Fig. 1. METHODS Cellular interaction of particles of different size, material and charge was studied in a triple cell co-culture model of the human airway wall to simulate the cellular part of the epithelial barrier, represented by AM, epithelial cells, and DC. 10,11 The cellular interplay after particle deposition was investigated by laser scanning microscopy (LSM) and the cellular response determined by measurement of TNF-a. Since nanoparticles have the size of small cell compo- nents their identification in the cytoplasm is difficult. Hence, we combined different microscopic techniques to visualize nanoparticles in the cytoplasm of cultured cells: (1) Fluor- escent particles were analyzed by LSM combined with PAEDIATRIC RESPIRATORY REVIEWS (2006) 7S, S73–S75 KEYWORDS particles; airway wall; surfactant; macrophages; dendritic cells Summary Inhaled particles may cause increased pulmonary and cardiovascular mor- bidity and mortality. The wall structures of airways and alveoli act as a series of structural and functional barriers against inhaled particles. Deposited particles are displaced and come into close association with epithelial cells, macrophages and dendritic cells. The cellular interplay after particle deposition in a triple cell co-culture model of the human airway wall was investigated by laser scanning microscopy. Furthermore, the cellular response was determined by measurement of TNF-a. Dendritic cells gained access to the apical side of the epithelium where they sampled particles and interacted with macro- phages. ß 2006 Elsevier Ltd. All rights reserved. * Corresponding author. Tel.: +41 31 631 8432; Fax: +41 31 631 3807. E-mail address: gehr@ana.unibe.ch (P. Gehr). 1526-0542/$ – see front matter ß 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.prrv.2006.04.169