Kinetics of Lung Macrophages Monitored in Vivo Following Particulate Challenge in Rabbits

Autor: Hazel A. Jones, Thomas Krausz, Geraldine E. Bolden, Ian Clark, Alan R. Boobis, John B. Schofield, C Haslett, Sven Valind
Rok vydání: 2002
Předmět:
Zdroj: Toxicology and Applied Pharmacology. 183:46-54
ISSN: 0041-008X
DOI: 10.1006/taap.2002.9462
Popis: The ligand PK11195 binds specifically in macrophages. We have assessed the use of positron emission tomography (PET) of [ 11 C]R-PK11195 to monitor macrophage disposition following particulate challenge to the lung. Repeated PET scanning was performed over 4 weeks following iv [ 11 C]R-PK11195 in rabbits treated with 5-μm particles of either amorphous (aSiO 2 ) or microcrystalline (xSiO 2 ) silica instilled into right upper pulmonary lobes. aSiO 2 resulted in increased macrophages, few neutrophils, and no fibrosis, while xSiO 2 increased macrophages and neutrophils and caused fibrosis. After both stimuli, 11 C localized to the challenged area and correlated with macrophage numbers. Radioactive counts in challenged/control lung regions peaked at 4 days for aSiO 2 (2.88, n = 2) and 6 days for xSiO 2 (4.62, n = 2). The signal remained elevated throughout the study (aSiO 2 , 2.33 ± 0.77 SD, n = 14; xSiO 2 , 3.99 ± 1.29 SD, n = 9), as did macrophage accumulation. 11 C also localized to regions consistent with macrophage traffic through lymph ducts 6 days after aSiO 2 challenge, but not until 4 weeks after xSiO 2 . Specific binding of R-PK11195 in macrophages was demonstrated by microautoradiography in lavage fluid from an inflamed rabbit knee-joint model. These data suggest that PET scanning after [ 11 C]PK11195 provides a new noninvasive approach for the study of macrophage kinetics in the lung.
Databáze: OpenAIRE
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