Adhesion molecules in glomerulonephritis

David J. Nikolic-Paterson, Ian W. Main, Hui Y. Lan, Prudence A. Hill, Robert C. Atkins

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Abstract

The infiltration and activation of leukocytes within the glomerulus and interstitium play a key role in the initiation and progression of glomerulonephritis. The recent characterization of cellular adhesion molecules has led to the identification of mechanisms by which leukocytes enter the kidney and subsequently interact with renal parenchymal cells. The therapeutic goal of intervening in the infiltration and activation of particular leukocyte populations can be approached by strategies that interrupt binding between specific pairs of adhesion molecules. The ability of anti-ICAM-1 antibody administration to intervene in experiment disease models [29, 39, 58] holds promise for treatment of human glomerulonephritis. Indeed, anti-ICAM-1 antibodies have already proven beneficial in human kidney transplantation [32]. There are many possible alternative therapeutic strategies that do not rely upon mAb therapy. One example is the administration of carbohydrate sialyl-Lewis X, a ligand for P-selectin, which suppresses acute neutrophil-dependent lung injury in rats [54]. Another approach is to block cytokines and other soluble mediators which, amongst other functions, stimulate up-regulation of adhesion molecule expression and leukocyte adhesion. Blockade of PAF action through use of specific antagonists has been shown to reduce injury in various experimental models and part of this effect can be attributed to inhibiting firm adhesion of PMNL to endothelium. Treatment with the IL-1 receptor antagonist can suppress progressive crescentic glomerulonephritis in the rat [43], while anti-IL-8 antibody treatment has been reported to prevent neutrophil-mediated acute glomerular injury in experimental immune complex glomerulonephritis [83]. In summary, the study of adhesion molecules has greatly increased our understanding of pathogenic mechanisms in glomerulonephritis and it holds tremendous potential for development of novel therapies.

Original languageEnglish
Pages (from-to)3-22
Number of pages20
JournalSpringer Seminars in Immunopathology
Volume16
Issue number1
DOIs
Publication statusPublished - 1 Jul 1994
Externally publishedYes

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