Immunophenotypic analysis of the aortic wall in Takayasu's arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions
Introduction
Takayasu's disease is a chronic non-specific arteritis affecting large arteries, especially the aorta, the aortic arch and its main branches, and is characterized by ocular disturbances and weakening of upper extremity pulses 1, 2, 3, 4. It predominantly affects young women and has a worldwide distribution with highest incidence in the East 1, 5. Autopsy examinations have demonstrated typical gross morphological alterations of the aorta with irregular wall thickening, intimal proliferation and fibrotic contraction of the media and adventitia associated with acute exudative inflammation, chronic non-specific productive inflammation, and various types of granulomatous inflammation 6, 7. However, the trigger for these inflammatory reactions in Takayasu's arteritis is unknown. Various aetiologies including genetic associations 8, 9, 10, infections [11]and autoimmune reactions 12, 13, 14, 15have been proposed.
The previous observations of the histological features and stages of progression of Takayasu's disease suggest that many factors may play a role in its aetiology 5, 7, 16, 17, 18. During the acute stage, the inflammatory process involves all layers of the vessel wall, as represented by the accumulation of lymphocytes, plasma cells and polymorphonuclear leucocytes [18]. The intermediate stage is characterized by intense hyperplasia of the vasa vasorum and progression of the inflammatory process within the outer media and adventitia. The terminal phase exhibits diffuse or nodular perivascular fibrosis and subsequent luminal narrowing 7, 18. However, when fibrosis is inadequate and delayed because of rapid progression of the disease, the wall may weaken and result in aneurysmal dilatation [7].
The involvement of dendritic cells in the immuno-inflammatory reactions associated with various vascular pathologies, including primary atherosclerotic lesions 19, 20, 21, atherosclerotic saphenous vein grafts [22]and venous pathologies [23], has been previously described, but their possible involvement in the inflammatory reactions in Takayasu's arteritis has not been investigated. Dendritic cells are known to represent a group of specialized cells that are responsible for initiating and modulating immune responses in pathological conditions 24, 25, 26, 27, 28. Dendritic cells function as potent antigen-presenting cells by internalizing, processing and presenting antigens to resting lymphocytes 24, 25, 26, 27, 28. Therefore, their possible involvement in Takayasu's disease is of interest.
Although the histological features of Takayasu's disease have been documented 5, 16, immunophenotypic analysis of the cellular composition of the arterial wall affected by this disease has not been previously performed. In this study, the cellular composition of the aortic wall in Takayasu's arteritis is investigated to evaluate the possible contribution of immuno-inflammatory cells in this vascular pathology.
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Materials and methods
Materials were collected in accordance with the principles outlined in the Declaration of Helsinki [29], and the present study was approved by the institutional review boards of St Vincent's Hospital, Sydney, Australia, and the National Cardiovascular Center, Osaka, Japan.
Results
All the aortic specimens were free of any atherosclerotic lesions but the superficial and middle layers of the intima were represented by a well-developed fibrous tissue. Cells forming the fibrous tissue stained positively for alpha-smooth muscle actin (Fig. 1A). In all the specimens, some areas of the fibrous tissue contained only remnants of dead cells embedded in the extracellular matrix (Fig. 1A).
Although fibrous tissue of the superficial and middle layers of the intima contained only a few
Discussion
Consistent with the data from earlier publications 7, 18, 31, the present study demonstrated that the accumulation of inflammatory cells in the deep portion of the intima and within the adventitia is a typical feature of Takayasu's disease. However, the degree of accumulation of immuno-inflammatory cells varied markedly between different specimens and the authors were not able to establish a correlation between the degree of inflammatory cell infiltration and the duration of disease (Table 1).
Acknowledgements
We thank the St Vincent's Clinic Foundation, Sydney, Australia for financial support.
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