Hisao Murata

Histopathological features of murine systemic vasculitis caused by Candida albicans extract--an animal model of Kawasaki disease.

AbstractObjective and Design: We examined the histopathological features of systemic vasculitis caused in mice by injection of a Candida albicans (C. albicans) extract and investigated the principal genetic roles in the development of vasculitis. Materials and Methods: C. albicans extract was injected intraperitoneally for five consecutive days in the 1st and 5th weeks to CD-1, C57BL/6N, C3H/HeN, BALB/cAnN, DBA/2N and CBA/JN mice. At week 8, mice were killed, and histological examination was performed by light microscopy. Results: Arteritis had developed in 66% of CD-1 mice. The extramural coronary arteries and aortic root close to the orifice of coronary arteries were most frequently involved. Histologically, the characteristic feature of the arteritis was proliferative and granulomatous inflammation accompanied by numerous macrophages, lymphocytes, plasma cells and neutrophils. Fibrocellular intimal thickening with destruction of the internal elastic lamina and media was also observed. Five mouse strains after injection of C. albicans extract were clearly classified into a resistant group (CBA/JN, DBA/2N and BALB/cAnN mice) and a sensitive group (C3H/HeN and C57BL/6N mice). The inbred mouse strains which showed the same histocompatibility-2 (H-2) haplotype exhibited a different susceptibility to development of vasculitis. Conclusion: This arteritis murine model shows unique histological features that have not been observed in other animal vasculitis models and it most closely resembles Kawasaki disease in humans. The genetic control of susceptibility to induction of vasculitis by the C. albicans extract is dependent to the mouse strains, but is not linked to the H-2 loci.

Experimental Candida-Induced Arteritis in Mice

An extract of Candida albicans isolated from a patient with typical mucocutaneous lymph node syndrome (MCLS) can produce coronary arteritis in a mouse when injected intraperitoneally. An unusual feature of this arteritis is that it is granulomatous, shows no fibrinoid change and is confined to the coronary arteries. These characteristics are quite similar to those found in patients with MCLS.

Candida albicans -Extract Causing Systemic Vasculitis in Mice as an Animal Model of Kawasaki Disease

We established a systemic vasculitis mice model involving coronary arteries using C. albicans-Extract. This model is evaluated as an animal model of Kawasaki disease (KD) since this model has many similar points of KD. Careful study of this model may provide fundamental information that increases our understanding of the pathogenesis, natural history, and appropriate therapy of this illness. Yeast cells of a C. albicans strain isolated from the feces of a KD patient were incubated at 37°C for 72 hours. After harvest, the extract was obtained from the yeast cells using boiling water and KOH. C. albicans-Extract suspended in PBS was injected intraperitoneally for five consecutive days at 1st and 5th week. At 9th week, mice were killed under anesthesia, and then, histological features of the arteritis in various organs were observed. There was a difference in susceptibility to vasculitis between inbred mice strains. BALB/c, DBA/2 and CBA/J mice were resistant to vasculitis, however, C3H/HeN and C57BL/6 mice were classified as sensitive strains. Coronary arteries were most frequently involved; aorta and other medium-sized arteries in kidney, retroperitoneum, testis etc. were sometimes involved. Vasculitis was defined as a productive inflammation, which shows dense infiltrates of large mononuclear cells and polymorphonuclear cells at the adventitia and/or media of arteries with an association of a few small round cells. Fibrinoid necrosis was rarely seen. Most of mononuclear cells and polymorphonuclear cells were positive for CD11b, and small round cells were positive for CD4, CD8a or CD45RB. ICAM-1 was usually expressed on endothelial cells of arteries. IFN-γ was expressed on small round cells and large mononuclear cells, but IL-12 and IL-4 were not expressed in any cells. An expression of TNF-α and IL-6 were usually demonstrated on large mononuclear cells, small round cells and endothelial cells.