Expression of heat shock protein-70 by dendritic cells in the arterial intima and its potential significance in atherogenesis.
OBJECTIVE
Overexpression of heat shock proteins (HSPs) is an important means of cell protection during physiologic stress such as occurs during atherogenesis. Immune responses are early events in atherosclerosis, with recent studies indicating that both humoral and cellular autoimmune processes in atherogenesis are directed toward HSPs. Dendritic cells are the key cells in the initiation and regulation of immune responses. This study examined whether HSP70 is overexpressed by dendritic cells in atherosclerotic lesions.


METHODS
Twenty-six carotid artery and 16 aortic specimens obtained at endarterectomy and aortic reconstruction were examined with immunohistochemical techniques. The nature of cells that overexpressed HSP70 was studied in consecutive sections that were double stained with antibodies to HSP70 and cell type-specific markers, including CD1a and fascin (to identify dendritic cells), CD14 (monocytes), CD68 (macrophages), CD3 (T cells), CD15 (mast cells), von Willibrand factor (endothelial cells), and alpha-smooth muscle actin (smooth muscle cells). Staining with HLA-DR and CD1d was used to identify cells involved in antigen presentation.


RESULTS
In advanced atherosclerotic lesions, several cell types, including monocytes, macrophages, dendritic cells, and smooth muscle cells, overexpressed HSP70. In contrast, in early atherosclerotic lesions, only dendritic cells overexpressed HSP70. Dendritic cells that overexpressed HSP70 frequently contacted T cells and also expressed HLA-DR. Furthermore, dendritic cells that clustered with T cells expressed CD1d, a unique molecule responsible for presenting lipid antigens.


CONCLUSIONS
The results suggest that direct contacts between activated dendritic cells that overexpress HSP70 and T cells might be responsible for T cell activation and might facilitate the presentation of lipid antigens to T cells directly within the arterial wall. In early intimal lesions, HSP70 is overexpressed exclusively by dendritic cells, which suggests that dendritic cells might be involved in the early phases of atherogenesis.
Bobryshev
Yuri V
YV
Surgical Professorial Unit, University of New South Wales, St Vincent's Hospital, Sydney, Australia. ybobryshev@stvincents.com.au
Lord
Reginald S A
RS
D000328:Adult; D000368:Aged; D001011:Aorta / Q000166:cytology / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism*; D001315:Australia; D002339:Carotid Arteries / Q000166:cytology / Q000473:pathology; D003713:Dendritic Cells / Q000378:metabolism*; D006681:HLA-D Antigens / Q000096:biosynthesis; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008854:Microscopy, Electron; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism; D017539:Tunica Intima / Q000166:cytology*
D006681:HLA-D Antigens; D018840:HSP70 Heat-Shock Proteins