Presentation: Pathogenesis of Allergic Granulomatous Angitis in the Experimental Model with Mice (2007)

2001 Pathogenesis of Allergic Granulomatous Angitis in the Experimental Model with Mice

Objective: Here we reported a murine model of allergic granulomatous angitis (AGA) and an investigation into its pathogenesis by the evaluation of differences in the immunological responses between two murine strains.
Methods: C57BL/6 and BALB/c mice were sensitized with ovalbumin (OVA). After the inhalation of OVA, we measured the cell number and cytokine concentration in the blood and bronchoalveolar lavage fluid (BALF). We also examined the histological changes of the pulmonary arteries for endothelial damage and vascular remodeling.
Results: The number of eosinophils increased in the blood and BALF in both strains; however, the number in C57BL/6 in BALF was significantly higher than that in BALB/c. Histological analysis demonstrated severe vasculitis of the pulmonary arteries with derangement of the muscle layer and smooth muscle cell hyperplasia in C57BL/6, and subsequently pulmonary arteries were highly occluded on the 3rd and 7th day of OVA exposure in C57BL/6 compared with BALB/c. Semi-quantitative analysis of the severity of vasculitis in pulmonary arteries revealed that the internal vascular space was highly reduced by smooth muscle hyperplasia in C57BL/6 compared to BALB/c mice.
The concentrations of interleukin (IL) -4, IL-5 and interferon (IFN)-γ in BALF of C57BL/6 were significantly high compared to those of BALB/c.
Conclusion: C57BL/6 mice exhibited severe allergic vasculitis with granuloma in the pulmonary arteries compared to BALB/c mice. The high concentrations of IL-4, IL-5 and IFN-γ in the lung may play a critical role in the pathogenesis of AGA in C57BL/6 mice.
Image: On the 7th day, small pulmonary artery in C57BL/6

Obliteration of pulmonary artery by mesenchymal cells
Spindle-like cells occupy the lumen of pulmonary artery. Infiltration of mononuclear cells and eosinophils, and glanuloma with multinuclear giant cells were observed around the artery. (HE staining)

 N. Sasaki, None; K. Yamauchi, None; H. Inoue, None; A. Kamataki, None; T. Sawai, None.