Print Email Facebook Twitter Alveolar macrophages suppress non-specific inflammation caused by inhalation challenge with trimellitic anhydride conjugated to albumin Title Alveolar macrophages suppress non-specific inflammation caused by inhalation challenge with trimellitic anhydride conjugated to albumin Author Valstar, D.L. Schijf, M.A. Arts, J.H.E. Kuper, C.F. Nijkamp, F.P. Storm, G. Bloksma, N. Henricks, P.A.J. TNO Kwaliteit van Leven Publication year 2006 Abstract Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter these inhaled compounds and were previously shown to affect TMA-induced asthma-like symptoms in the Brown Norway rat (Valstar et al., Toxicol. Appl. Pharmacology 211:20-29, 2006). TMA is a hapten that will bind to endogenous proteins upon entrance of the body. Therefore, in the present study we determined if TMA conjugated to albumin is able to induce asthma-like symptoms and if these are affected by AM depletion. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day prior to the inhalation challenge the rats were treated intratracheally with either empty liposomes or liposomes containing clodronate (dichloromethylene diphosphonate) to specifically deplete the lungs of AMs. On day 21, all groups of rats were challenged by inhalation of TMA-BSA. Breathing frequency, tidal volume, and minute ventilation were measured before, during, within 1 h, and 24 h after challenge and the gross respiratory rate score was determined during challenge. Total and TMA-specific IgE levels were determined in serum and lung lavage fluid and parameters of inflammation and tissue damage were assessed in lung lavage fluid and/or lung tissue 24 h after challenge. Sensitization with TMA had no effect on the lung function before challenge, but TMA-BSA challenge resulted in an early asthmatic response as compared to the non-sensitized rats, irrespective of AM depletion. AM depletion had no effect on the sensitization-induced serum and lung lavage fluid IgE levels. TMA-BSA inhalation did not induce airway inflammation and tissue damage irrespective of sensitization, unless AM were depleted. Data indicate that AMs inhibit immunologically non-specific damage and inflammatory cell influx into the lungs as caused by TMA-BSA inhalation. Since effects of inhalation challenge with TMA-BSA are partly different from those of TMA, challenge with the latter is to be preferred for hazard identification. © Springer-Verlag 2006. Subject HealthToxicology and Applied PharmacologyAirway inflammationAlveolar macrophagesEarly asthmatic responseOccupational asthmaTrimellitic anhydridealbuminclodronic acidimmunoglobulin Eliposometrimellitic anhydrideanimal experimentanimal modelanimal tissuearticlecontrolled studyfemaleinflammationinflammatory cellinhalationlung alveolus macrophagelung fluidlung functionlung lavagelung minute volumenonhumanoccupational asthmaoccupational exposurepriority journalratsensitizationtidal volumeAllergensAnimalsAsthmaBone Density Conservation AgentsBronchial HyperreactivityBronchoalveolar Lavage FluidCattleClodronic AcidCytokinesDrug Therapy, CombinationFemaleHaptensImmunoglobulin ELiposomesMacrophages, AlveolarOccupational DiseasesPhthalic AnhydridesProtein BindingRatsRats, Inbred BNRespiratory Function TestsSerum Albumin, BovineRattus norvegicus To reference this document use: http://resolver.tudelft.nl/uuid:510d71c9-78de-4b97-b38b-e3974684a1a9 DOI https://doi.org/10.1007/s00204-006-0081-5 TNO identifier 239464 ISSN 0340-5761 Source Archives of Toxicology, 80 (9), 561-571 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.