Targeting Leukocytes in Immune Glomerular Diseases
The glomerulonephritides are a collection of separate diseases with differing pathogeneses that collectively are common and important causes of renal disease. Effective, non-toxic immunomodulatory treatments for glomerulonephritis are lacking. This review will focus on our understanding of the role of leukocytes in immune glomerular disease, specifically in severe and rapidly progressive forms of glomerulonephritis, and provide examples of potential therapeutic targets. The glomerulus is a high flow, high pressure capillary plexus bounded by arterioles that is vulnerable to a variety of immune or inflammatory insults. The variety in the pathogenesis of different forms of glomerulonephritis, together with the capacity of both humoral and cellular effector arms to induce injury, means that understanding the pathogenesis of glomerulonephritis is necessary to effectively apply new treatments. Leukocytes are involved in the pathogenesis of glomerulonephritis at several levels, including the loss of tolerance, adaptive immune responses directed by T cells, cellular effectors inducing injury in delayed type hypersensitivity-like reactions, and by macrophage/neutrophil recruitment via the deposition of circulating immune complexes or in situ immune complexes. Evidence is emerging that anti-neutrophil cytoplasmic antibodies activate neutrophils, leading to glomerular capillaritis. Some therapeutic options limit local inflammation, while others modify the underlying pathogenetic immune response. Areas of current interest include the relationship between infiltrating and local cells, limiting effector cell activation, particularly macrophages; as well as understanding and targeting leukocyte recruitment to this unique vasculature. Modifying pathogenetic T or B cells also is a promising strategy in both systemic autoimmunity affecting the kidney and organ specific autoimmunity.
No Supplementary Data
No Article Media
Document Type: Research Article
Affiliations: Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre,246 Clayton Rd, Clayton, VIC 3168, Australia.
Publication date: 2008-02-01
More about this publication?
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.