Leukocyte-endothelial interactions in antineutrophil cytoplasmic antibody-associated systemic vasculitis.
ABSTRACT The etiology of ANCA-associated vasculitis is unknown. Currently, it is believed that disease may be triggered by infection with the release of proinflammatory cytokines in genetically susceptible individuals. Priming of PMNs and endothelial cells by these cytokines allows ANCAs to activate PMNs, with damage localized to the endothelium, resulting in early lesions. Damage and activation of endothelial cells produces proinflammatory chemokines and cytokines with influxes of monocytes and T cells that intensify endothelial damage. In the kidney, these changes eventually lead to crescent formation. Antigen-specific memory T cells persist after disease remission with the potential of reactivation and disease relapse. Although our understanding of the pathophysiologic mechanisms of ANCA-associated vasculitis is far greater now than when ANCAs were first identified in 1982, more experimental work in combination with clinical observations is required to further elucidate these mechanisms.
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ABSTRACT: It was reported previously that a Candida albicans water-soluble fraction (CAWS), including a mannoprotein and β-glucan complex, has strong potency in inducing fatal necrotizing arteritis in DBA/2 mice. In this study, histopathological changes and cardiac function were investigated in this system. One mg/day of CAWS was given to DBA/2 mice via peritoneal injection for five days. The CAWS-treated DBA/2 mice were induced aortitis and died at an incidence of 100% within several weeks. Histological findings included stenosis in the left ventricular outflow tract (LVOT) and severe inflammatory changes of the aortic valve with fibrinoid necrosis. Cardiomegaly was observed and heart weight increased 1.62 fold (P < 0.01). Echocardiography revealed a severe reduction in contractility and dilatation of the cavity in the left ventricle (LV): LV fractional shortening (LVFS) decreased from 71% to 38% (P < 0.01), and the LV end-diastolic diameter (LVDd) increased from 2.21 mm to 3.26 mm (P < 0.01). The titer of BNP mRNA increased in the CAWS-treated group. Severe inflammatory changes resulting from CAWS brought about lethal LV dysfunction by aortic valve deformation with LVOT stenosis. This system is proposed as an easy and useful experimental model of heart failure because CAWS arteritis can be induced by CAWS injection alone.International journal of vascular medicine 01/2012; 2012:570297.
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ABSTRACT: Anti-neutrophil cytoplasm antibody associated vasculitides are autoimmune diseases that require treatment with powerful immunosuppressants in order to avert life threatening complications, principally renal failure and lung haemorrhage. Their pathogenesis remains unclear but the circulating autoantibodies are almost certainly instrumental in mediating vascular inflammation. Recent insights into leukocyte-autoantibody interactions support this assertion and may direct future therapeutic strategies, perhaps circumventing some of the toxicity associated with currently used drugs.The International Journal of Biochemistry & Cell Biology 04/2003; 35(3):277-82. · 4.15 Impact Factor
Article: The systemic vasculitides.[Show abstract] [Hide abstract]
ABSTRACT: Taken together, the systemic vasculitides constitute a small but significant component in the practice of many primary care physicians. Like most diseases with autoimmune aspects, the vasculitides increase in prevalence with age. Of paramount importance is careful differentiation, to provide early appropriate treatment and to monitor adverse effects.Hospital practice (Office ed.) 08/1992; 27(7):77-81, 85-6, 88.