Recent Insights into the Mechanisms of Vascular Injury
Vascular injury and inflammation are the most important features of a heterogeneous group of disorders commonly referred to as the systemic necrotizing vasculitides.1 Previous studies have established two pathogenetic mechanisms for vasculitis2,3: deposition of circulating immune complexes with subsequent complement activation and inflammation; and interactions between circulating antibodies with blood vessel wall antigens in situ, such as occurs in Goodpasture’s syndrome, in which autoantibodies interact with glomerular and pulmonary capillary basement membranes. These mechanisms, however, cannot account for many forms of inflammatory vasculitis and several additional or alternative pathways have recently been explored. In this chapter we will review three settings of vascular injury which may shed light on the pathogenesis of vasculitis. First, we will examine the role of cytokine-induced activation4 of endothelial cells in causing endothelial and vascular injury and the possible role of these effects in one form of vasculitis—Kawasaki’s disease; second, we will describe the details of vascular injury occurring during transplantation reactions, and how these may be relevant to other forms of vasculitis; and third, we will review recent work associating the presence of antineutrophil cytoplasmic antibodies with certain forms of vasculitis, such as Wegener’s granulomatosis.
KeywordsKawasaki Disease Heparan Sulfate Vascular Injury Antineutrophil Cytoplasmic Antibody Hyperacute Rejection
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