Respiratory tract responses to dust: Relationships between dust burden, lung injury, alveolar macrophage fibronectin release, and the development of pulmonary fibrosis

Journal Article · Mon Oct 01 00:00:00 EDT 1990 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(90)90109-8· OSTI ID:6065481

Driscoll, K E; Maurer, J K; Lindenschmidt, R C; Romberger, D; Rennard, S I; Crosby, L ^[1]

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1. Procter Gamble Company, Cincinnati, OH (USA)

A multidisciplinary approach was used to investigate the responses of the respiratory tract to silica (SiO2) or titanium dioxide (TiO2). Rats were intratracheally instilled with 5-100 mg/kg of dust and bronchoalveolar lavage fluid (BALF) lactate dehydrogenase (LDH) and total protein (TP) and ex vivo alveolar macrophage (AM) fibronectin release assessed on Days 7, 14, and 28 after exposure. Lung dust burdens were determined on Days 1, 7, and 28 after instillation. Both dusts elicited dose-related increases in BALF LDH and TP, a response which was more pronounced and progressive with SiO2. All doses of SiO2 elicited persistent increases in AM fibronectin release. TiO2 stimulated persistent increases in AM fibronectin release at greater than or equal to 50 mg/kg, with transient or no effect at less than or equal to 10 mg/kg. Increased SiO2 retention was observed for all doses and TiO2 retention was increased only at doses greater than or equal to 50 mg/kg. In vitro exposure of naive AM to SiO2 or TiO2 did not stimulate AM fibronectin release. Histopathology demonstrated fibrosis at all SiO2 doses; only TiO2 doses greater than or equal to 50 mg/kg resulted in fibrosis. These results reveal an association between increased dust retention, lung injury, activation of AM fibronectin release, and the development of fibrosis. The magnitude and temporal pattern of responses clearly differentiated SiO2 from TiO2. The correlation of BALF markers of lung injury and increased AM fibronectin release with the development of fibrosis supports the use of these parameters as predictive biomarkers of dust-induced interstitial lung disease.

• OSTI ID: 6065481
• Journal Information: Toxicology and Applied Pharmacology; (USA), Vol. 106:1; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
DUSTS
TOXICITY
RESPIRATORY SYSTEM
SENSITIVITY
RESPIRATORY SYSTEM DISEASES
BIOLOGICAL MARKERS
DOSE-RESPONSE RELATIONSHIPS
FIBROSIS
INHALATION
LACTATE DEHYDROGENASE
LAVAGE
MACROPHAGES
PROTEINS
RATS
RETENTION
SILICA
TITANIUM OXIDES
ANIMAL CELLS
ANIMALS
CHALCOGENIDES
CONNECTIVE TISSUE CELLS
DISEASES
ENZYMES
HEMIACETAL DEHYDROGENASES
INTAKE
MAMMALS
MINERALS
ORGANIC COMPOUNDS
OXIDE MINERALS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
PHAGOCYTES
RODENTS
SILICON COMPOUNDS
SILICON OXIDES
SOMATIC CELLS
TITANIUM COMPOUNDS
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology