Rheumatology (Oxford, England) · 2003
MRL/lpr lupus-prone mice show exaggerated ICAM-1-dependent leucocyte adhesion and transendothelial migration in response to TNF-alpha.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Marshall D, Dangerfield J P, Bhatia V K, Larbi K Y, Nourshargh S, Haskard D O
Аннотация
OBJECTIVE: Endothelial activation and dysfunctional leucocyte-endothelial interactions are thought to play key roles in the pathogenesis of systemic lupus erythematosus (SLE). The object of this study was to investigate directly the effect of increased endothelial adhesion molecule expression on leucocyte-endothelial cell interactions, using the MRL/lpr mouse model.
METHODS: Leucocyte rolling, arrest and transendothelial migration were quantified in the cremaster muscle microcirculation of 20-week-old MRL/lpr mice, using intravital microscopy. Endothelial adhesion molecule expression was quantified using intravenously injected radiolabelled monoclonal antibodies.
RESULTS: Basal expression of intercellular adhesion molecule 1 (ICAM-1) by cremaster endothelium was 2-fold greater in MRL/lpr than in MRL/++ mice (P<0.05). There was a 1.6-fold increase in expression of vascular adhesion molecule 1 (VCAM-1), but no increase in E-selectin or P-selectin expression. Following intrascrotal injection of saline, no difference was detected in leucocyte-endothelial interactions between MRL/lpr and control MRL/++ mice. In contrast, intrascrotal injection of tumour necrosis factor alpha (TNF-alpha) (2 h test period) led to significantly increased numbers of adherent and extravasated leucocytes in MRL/lpr (5.98+/-0.71 and 5.45+/-0.34 leucocytes per 100 micro m vessel segment respectively) compared with MRL/++ mice (3.63+/-0.26 and 2.97+/-0.24 respectively, each P<0.05). Treatment of TNF-alpha-stimulated mice with anti-ICAM-1 F(ab')2 (YN1) abolished the difference between MRL/lpr and MRL/++ mice, whereas a negative control anti-DNP F(ab')2 had no effect.
CONCLUSIONS: MRL/lpr lupus-prone mice show exaggerated ICAM-1-dependent leucocyte-endothelial interactions in response to TNF-alpha. Increased leucocyte-endothelial interactions due to endothelial priming could contribute to the clinical link between infection and flares of lupus disease activity.
METHODS: Leucocyte rolling, arrest and transendothelial migration were quantified in the cremaster muscle microcirculation of 20-week-old MRL/lpr mice, using intravital microscopy. Endothelial adhesion molecule expression was quantified using intravenously injected radiolabelled monoclonal antibodies.
RESULTS: Basal expression of intercellular adhesion molecule 1 (ICAM-1) by cremaster endothelium was 2-fold greater in MRL/lpr than in MRL/++ mice (P<0.05). There was a 1.6-fold increase in expression of vascular adhesion molecule 1 (VCAM-1), but no increase in E-selectin or P-selectin expression. Following intrascrotal injection of saline, no difference was detected in leucocyte-endothelial interactions between MRL/lpr and control MRL/++ mice. In contrast, intrascrotal injection of tumour necrosis factor alpha (TNF-alpha) (2 h test period) led to significantly increased numbers of adherent and extravasated leucocytes in MRL/lpr (5.98+/-0.71 and 5.45+/-0.34 leucocytes per 100 micro m vessel segment respectively) compared with MRL/++ mice (3.63+/-0.26 and 2.97+/-0.24 respectively, each P<0.05). Treatment of TNF-alpha-stimulated mice with anti-ICAM-1 F(ab')2 (YN1) abolished the difference between MRL/lpr and MRL/++ mice, whereas a negative control anti-DNP F(ab')2 had no effect.
CONCLUSIONS: MRL/lpr lupus-prone mice show exaggerated ICAM-1-dependent leucocyte-endothelial interactions in response to TNF-alpha. Increased leucocyte-endothelial interactions due to endothelial priming could contribute to the clinical link between infection and flares of lupus disease activity.