Macrophage migration inhibitory factor (MIF)--potential perspectives for immune-intervention in renal disease.
نویسندگان
چکیده
corticoids [6 ]. Indeed, MIF is the only molecule known Introduction to over-ride the anti-inflammatory action of glucocorticoids, putting MIF at a key point in the regulation of Macrophage and T-cell infiltration occurs in virtually the inflammatory and immune responses. all forms of human glomerulonephritis [1]. The degree of renal impairment correlates with macrophage and T-cell accumulation, arguing that immune cellmediated injury is a common mechanism in the progression of glomerulonephritis. This hypothesis is supported by animal studies in which various depletion Macrophage migration inhibitory factor in strategies have demonstrated a pathological role for glomerulonephritis macrophages and T cells in experimental models of glomerulonephritis. We know little of the specific antiMIF mRNA and protein are expressed constitutively gens involved in the cellular immune response within in many tissues [7]. The 12 kDa MIF protein is the kidney, therefore we reasoned that the best strategy encoded by a single gene and the protein product is for immune-intervention in glomerulonephritis is to stored within the cytoplasm, being released when cells target the molecules which operate at the pinnacle of are stimulated by factors such as lipopolysaccharide. the immune and inflammatory cascades. This led us to In normal kidney, MIF is expressed constitutively by study the role of MIF in kidney disease. some glomerular and tubular epithelial cells. During the development of rat crescentic anti-glomerular basement membrane glomerulonephritis, there is marked up-regulation of MIF expression by intrinsic kidney cells, including endothelium and glomerular and tubular epithelial cells [8]. Importantly, macrophage accumulation is localized exclusively in areas of strong What is macrophage migration inhibitory factor? MIF expression, contributing to focal glomerular and tubulointerstitial lesion formation. In preliminary Macrophage migration inhibitory factor (MIF) was studies, we have also shown that MIF expression is first described as a product of activated lymphocytes up-regulated in human glomerulonephritis, with strong over 30 years ago, but the functions of this molecule MIF expression in areas of macrophage infiltration. are only now being delineated [2]. The importance of MIF in the induction of the skin delayed-type hypersensitivity (DTH) response was recently confirmed in mice by administration of a neutralizing anti-MIF monoclonal antibody (mAb) [3]. In addition, MIF plays a central role in endotoxaemia and MIF collaborThe effect of anti-MIF antibody treatment on ates in primary T-cell activation [4,5]. Furthermore, a experimental glomerulonephritis novel and potentially very important finding is the ability of MIF to counter-regulate the action of glucoTo explore the therapeutic potential of blocking MIF, we administered a neutralizing anti-MIF mAb in a rat model of crescentic anti-GBM glomerulonephritis. Correspondence and offprint requests to: Dr Hui Y. Lan, Department Compared with administration of the control mAb, of Nephrology, Monash Medical Centre, Clayton Road, Clayton, Victoria 3168, Australia. treatment with the anti-MIF mAb over days 0–14 of
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ورودعنوان ژورنال:
- Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
دوره 13 11 شماره
صفحات -
تاریخ انتشار 1998