ICAM-1 expression on endothelium and systemic cytokine production in cutaneous neutrophilic leukocytoclastic vasculitis in NZBxNZWF1 mice

Abstract

The present study has examined relationship between cutaneous microvessel injury and adhesion molecule expression on the endothelium by cytokines in NZBxNZWF1 (B/WF1) mice, a model for human systemic lupus erythematosus. In advanced ages associated with overt clinical manifestation, but not in early ages, neutrophils with a minor proportion of monocytes and lymphocytes mainly adhered to the endothelium of capillary and the venule with fragmentation (leukocytoclasis), leading to the vascular injury (leukocytoclastic vasculitis). This was confirmed by the leak of monstral blue from the blood vessel. At this stage LFA-1+ leukocytes adhered to intensely expressed ICAM-1 on the endothelium, and this was paralleled with a significant rise in IL-1 alpha and TNF-alpha in the circulation. The present study suggests that IL-1 alpha and TNF-alpha may, at least in part, be responsible for the increased ICAM-1 expression on endothelium in cutaneous microvessels, resulting in the vascular injury characterized by neutrophilic leukocytoclasis in B/WF1 mice.