ovalbumin and Vasculitis

Currently, there are several animal models for vasculitis. Ovalbumin and lipopolysaccharide (OVA, LPS) are well established for causing inflammation and used as an adjunct in the vasculitis induction. However, to date, none has established the effect of OVA and LPS in disease induction. Therefore, in the present study, an attempt has been made to develop a new animal model for vasculitis using OVA/LPS in rats.. A total of 42 Wistar rats were divided randomly into seven groups (n=6/group), normal control, and three different doses (0.5, 1, and 5 mg/kg) of OVA and LPS treated groups. Half of the rats in each group received only intraperitoneal sensitization, while the remaining half rats were additionally subjected to a one-week intranasal challenge.. Results showed that both OVA/LPS in their respective groups have significantly increased circulating inflammatory cells, C-reactive protein (CRP), Inflammatory cytokines (IL-1β, IL-6, TNF-α), Kidney damage markers (BUN, Creatinine), and liver function enzymes (AST, ALT) in a dose-dependent manner.. OVA/LPS induced vascular inflammation in a dose-dependent manner. However, the higher (5 mg/kg) dose of ovalbumin and lipopolysaccharide has contributed to severe vascular inflammation through increasing inflammatory cytokines. These findings suggest that OVA/LPS may contribute as a possible model for vasculitis in rats.

Topics: Animals; Cytokines; Disease Models, Animal; Inflammation; Lipopolysaccharides; Ovalbumin; Rats; Rats, Wistar; Vasculitis

We investigated the effects of pan-class I PI3K inhibitor, ZSTK474 on vascular remodeling using a murine model of allergic vasculitis with eosinophil infiltration.. C57BL/6 mice were sensitized with OVA. The positive controls were exposed to aerosolized OVA daily for 7 days. The other group of mice were administered ZSTK474 (30 mg/kg, p.o. daily) in parallel with daily exposure to aerosolized OVA for 7 days. On the 3rd and 7th day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for pathological analysis. Cell differentials were determined and the concentrations of IL-4, IL-5, IL-13 and TGF-βin BAL fluid were measured.. The total cell numbers and eosinophil numbers in BALF were greatly reduced in the ZSTK474-treated group on the 3rd and 7th day after exposure to OVA. The numbers of total white blood cells and eosinophils in the peripheral blood were significantly reduced in the ZSTK474-treated group on the 3rd and 7th day after exposure to OVA. The concentrations of IL-4, IL-5, and IL-13 in BAL fluids were also reduced significantly on the 3rd day in the ZSTK474-treated group. The concentrations of TGF-β in BAL fluids were also reduced significantly on the 3rd and 7th day in the ZSTK474-treated group. The pathological scores reduced significantly in the ZSTK474-treated group compared to the control group.. The PI3K inhibitor, ZSTK474 suppressed pulmonary vascular remodeling in the murine model of allergic vasculitis with eosinophil infiltration. PI3K signal transduction may have a critical role in the immunological process that induces allergic vasculitis.

Topics: Animals; Asthma; Disease Models, Animal; Eosinophils; Female; Hypersensitivity; Inflammation; Interleukin-13; Interleukin-4; Interleukin-5; Leukocyte Count; Lung; Mice; Mice, Inbred C57BL; Ovalbumin; Phosphoinositide-3 Kinase Inhibitors; Transforming Growth Factor beta; Triazines; Vascular Remodeling; Vasculitis

Imatinib mesylate (IM) is a potent and specific tyrosine inhibitor and has been reported to inhibit mesenchymal cell proliferation in pulmonary fibrosis. In the present study, we examine the effects of IM on vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration.. C57BL/6 mice were sensitized with ovalbumin (OVA) and alum. The positive controls were exposed to aerosolized OVA daily for 7 days. IM treated mice with exposure to OVA were administered IM in parallel with daily exposure to aerosolized OVA for 7 days. On the 7th day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for pathological analysis. Cell differentials were determined and the concentrations of cytokines in the BAL fluid (BALF) were measured. Semi-quantitative analysis of pathological changes in the pulmonary arteries was evaluated according to the criteria of severity of vasculitis. Immunohistochemistry for Ki-67 to detect proliferating cells was performed.. The number of eosinophils in BALF was reduced significantly in the IM-treated group compared to the positive control. There was no significant difference in the concentrations of interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, tumor growth factor (TGF)-β or platelet-derived growth factor in the BAL fluid between the positive control and the IM-treated group. The pathological scores of vasculitis and the ratio of Ki-67-positive intra-luminal cells were reduced significantly in the IM-treated group compared to the control group after OVA exposure.. IM-suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration.

Topics: Administration, Inhalation; Administration, Oral; Animals; Benzamides; Bronchoalveolar Lavage Fluid; Cell Proliferation; Comorbidity; Cytokines; Disease Models, Animal; Eosinophils; Female; Imatinib Mesylate; Mice; Mice, Inbred C57BL; Myofibroblasts; Ovalbumin; Piperazines; Protein Kinase Inhibitors; Pyrimidines; Respiratory Hypersensitivity; Vasculitis

The allergen-unchallenged enteric lesions in late allergic asthma are largely unknown. To clarify this point, BALB/c mice were sensitized by ovalbumin (OVA)/aluminum adjuvant intraperitoneally two times (on days 0 and 10) and then challenged with OVA intranasally on day 14 (asthma group). Four days after the challenge, small intestinal lesions were examined. By this treatment, diarrhea was not observed in the asthma group. Compared to the controls with or without OVA sensitization and/or OVA challenge, the asthma group developed eosinophilic venulitis without an increase in mucosal mast cells in small intestines, whereas intestinal epithelial cells were relatively intact. A few numbers of interleukin (IL)-4(+) and IL-5(+) lymphoid cells were recognized in intestines in the asthma group, but not in the controls. Expression of vascular cell adhesion molecule-1 on venular endothelium and eotaxin-2(+) eosinophils, but not epithelial cells, in intestines were detected in the asthma group, but not in the controls. Total IgE, OVA-specific IgE and eotaxin, and IL-5, but not interferon-γ, were produced systemically in the asthma group compared to the controls. The present study suggests that eosinophilic venulitis without mast cells in the intestine may be induced by the systemic, but not by local, helper T 2-type responses. In addition, eosinophilic venulitis in small intestines may be subclinical enteric lesions.

Topics: Animals; Asthma; Chemokine CCL11; Disease Models, Animal; Eosinophilia; Female; Immunoglobulin E; Interferon-gamma; Interleukin-5; Intestine, Small; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Vasculitis; Venules

Here the authors report pulmonary allergic vasculitis with eosinophil infiltration in an asthma model of mice and investigated its pathogenesis. C57BL/6 and BALB/c mice were sensitized with ovalbumin (OVA). After the inhalation of OVA, the authors measured the cell number and cytokine concentration in the blood and bronchoalveolar lavage fluid (BALF). The authors also examined the histological changes of the pulmonary. 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. Semiquantitative analysis of the severity of vasculitis in the 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)-gamma in BALF of C57BL/6 were significantly high compared to those of BALB/c. C57BL/6 mice exhibited severe allergic vasculitis in the pulmonary arteries compared to BALB/c mice. The high concentrations of IL-4, IL-5, and IFN-gamma in the lung may play a critical role in the pathogenesis of allergic vasculitis in C57BL/6 mice.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Eosinophilic Granuloma; Female; Immunoglobulin E; Interferon-gamma; Interleukin-4; Interleukin-5; Leukocyte Count; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Pulmonary Artery; Vasculitis