title: Human alveolar macrophage phagocytic function is impaired by aggregates of ultrafine carbon particles.
abstract: Alveolar macrophages (AM) were collected by bronchoalveolar lavage from healthy volunteers. The AM were loaded with small masses (0.03-3 microg/10(6) AM) of ultrafine carbon particle aggregates. The phagocytic activity of the cells was studied 20 h after the loading. Fluorescein-labeled silica particles (3 microm) were used as test particles and the attachment and ingestion processes were studied separately. In some experiments, AM were incubated with interferon-gamma (IFN-gamma) for 20 h before and during the test of phagocytic activity and during measurement of oxidative metabolism. The ingested carbon particles induced a dose-related impairment of both the attachment and the ingestion processes with a marked impairment down to a carbon particle dose around 0.2 microg/10(6) AM. Such levels should reasonably occur after inhalation of existing concentrations of urban air particles, which to a considerable extent consist of aggregates of ultrafine particles with a carbon skeleton. Incubation with IFN-gamma (12.5 U/ml) also induced significant impairments in both the attachment and the ingestion processes. Loading with carbon further aggravated the effect of IFN-gamma. In contrast to earlier studies in rat AM, IFN-gamma did not impair the oxidative metabolism at rest in these human AM; instead the oxidative metabolism was increased. This difference was due to a difference between rat and human AM and not between rat and human IFN-gamma. Our results suggest that ingested environmental particles in AM, e.g., after an episode of high particle concentration, may impair phagocytic capacity of the cells, especially after infections that induce an increased production of IFN-gamma. Consequently, there might be a risk for additional infections. Moreover, inhaled particles not phagocytized by AM might damage the lung tissue.
authors.affiliation: Division of Inhalation Toxicology, Karolinska Institutet, Stockholm, Sweden. Margot.Lundborg@imm.ki.se
authors.forename: M
authors.initials: M
authors.lastname: Lundborg
authors.forename: U
authors.initials: U
authors.lastname: Johard
authors.forename: L
authors.initials: L
authors.lastname: Låstbom
authors.forename: P
authors.initials: P
authors.lastname: Gerde
authors.forename: P
authors.initials: P
authors.lastname: Camner
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002244:Carbon / Q000494:pharmacology*; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D012822:Silicon Dioxide / Q000378:metabolism; D013045:Species Specificity; D013481:Superoxides / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D013481:Superoxides; D009580:Nitroblue Tetrazolium; D002244:Carbon; D012822:Silicon Dioxide; D007371:Interferon-gamma