[Pathogenesis of primary large vessel arteritis].
Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are the two primary large-vessel arteritides. Recent advances in cellular immunology have allowed better understanding of pathogenesis of these diseases. In GCA and TA, resident adventitial dendritic cells are activated by unidentified stimuli. This activation induces chemokine synthesis which enhances recruitment of inflammatory cells. T-cells infiltrate the vascular wall and specifically recognize one or a few antigens presented by shared epitopes associated with specific HLA molecules on dendritic cells. Activated T-cells produce IFNgamma stimulating two distinct populations of macrophages. Macrophages located in the intima produce pro-inflammatory cytokines (IL-1, IL-6). Macrophages located in the media differentiate into giant cells and/or produce reactive oxygen species, nitric oxide and matrix metallo-proteinases. Macrophages of the media also produce VEGF, which leads to neovascularization and PDGF, which induces intimal hyperplasia and vascular occlusion. In TA, cytotoxic T cells infiltrate the vascular wall and induce apoptosis of the vascular cells. Better understanding of the pathogenesis of large-vessel arteritis may lead to development of immunosuppressive drugs specifically targeting the immunological mechanisms implicated in GCA and TA.
Arnaud
L
L
Service de médecine interne 2, hôpital Pitié-Salpêtrière, AP-HP, université Paris-6, 47-83, boulevard de l'hôpital, 75651 Paris cedex 13, France.
Haroche
J
J
Duhaut
P
P
Piette
J-C
JC
Amoura
Z
Z
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D013700:Giant Cell Arteritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D013625:Takayasu Arteritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*
D016207:Cytokines; D006680:HLA Antigens