BETA(1) AND BETA(3) INTEGRIN UP-REGULATION IN RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

The expression and distribution pattern of beta(1)(alpha(1)-alpha(6)) and alpha(v) beta(3) integrins and ICAM-1 and VCAM-1 counter receptors were evaluated by an immunohistochemical technique on eight renal samples from patients affected by rapidly progressive glomerulonephritis (RPGN) of different aetiologies. In ail cases integrins and counterreceptors displayed similar patterns. On tubular cells of renal cortex, a marked upregulation of alpha(2) beta(1), alpha(3) beta(1), alpha(5) beta(1), alpha(v) beta(3) integrins and VCAM-1 was observed with as many as 60-90% of tubular cross-sections labelled, while a strong ICAM-1 reactivity was limited to the luminal surface. The same adhesion molecules were also uniformly expressed on crescentic cells. In glomeruli, integrin upregulation occurred only on apparently preserved capillary tufts, i.e. in an early stage of lesion, while collapsed and sclerotic tufts showed a reduced integrin expression. In addition a morphometric study of extracellular matrix (EM) proteins cellular fibronectin and tenascin showed a 9.56+/-1.9-fold and 3.35+/-0.6-fold increase respectively in these proteins, as compared to normal kidney (P < 0.001). The upregulation of alpha(v) beta(3) on podocytes might play a role in the adhesion of crescentic cells. An increased production of cytokines, in particular transforming growth factor-beta, might induce augmented deposition of EM proteins and upregulation of beta(1) and beta(3) integrins in RPGN.