Alterations in leucocyte trafficking in lupus-prone mice: an examination of the MRL/faslpr mouse.
Systemic lupus erythematosus (SLE) is an autoimmune disease involving inappropriate inflammatory responses in a wide range of organs. The recruitment of leucocytes to these sites of inflammation is one of the key events in the development of tissue injury in SLE. However, the mechanisms responsible for this aberrant recruitment are poorly understood. Several studies have demonstrated upregulation of endothelial adhesion molecule expression in tissue biopsies from SLE patients. However, the progression to analysis of the functional roles of these adhesion molecules has entailed the use of animal models of SLE. Much of this work has involved the use of the MRL/faslpr mouse model of systemic autoimmune disease. This mouse develops a systemic inflammatory disease with similarities to human SLE. This review summarizes work by our laboratory and others which have examined alterations in the mechanisms of leucocyte trafficking in the MRL/faslpr mouse. These experiments have revealed upregulation of key adhesion molecules, alterations in leucocyte-endothelial cell interactions and in some cases protective effects of deletion of endothelial adhesion molecules. From analysis of a range of microvasculatures in the MRL/faslpr mouse, it is becoming clear that the roles of specific adhesion molecules vary according to the tissue under analysis. Furthermore, analysis of MRL/faslpr mice with targeted deletions of specific adhesion molecules indicates that their roles in development and progression of disease can vary from having key contributions to the development of disease, to attenuating disease via as yet unidentified mechanisms.
Hickey
Michael J
MJ
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Melbourne, Victoria, Australia. michael.hickey@med.monash.edu.au
D000818:Animals; D002465:Cell Movement; D004195:Disease Models, Animal; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology
D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1