Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats

Background. Galectins are characterized by specific affinity for beta -gala ctoside sugars, and they play a role in diverse biological processes, inclu ding cell adhesion, cell proliferation, and apoptosis. Galectin-1, -3, and -9 have been implicated in modulating the immune response. Methods. Nephrotoxic serum nephritis, which is characterized by crescent fo rmation and glomerular influx of CD8(+) cells into glomerular capillaries, was induced in Wistar Kyoto (WKY) rats by injecting rabbit antiglomerular b asement membrane serum. Following induction, the rats were treated either w ith phosphate-buffered saline or dexamethasone, galectin-1, galectin-3, or galectin-9 on alternate days and were sacrificed at day 14. At day 8, splen ic lymphocytes were isolated and employed for terminal deoxytransferase-med iated uridine triphosphate nick end-labeling (TUNEL) assay to assess the de gree of apoptosis, and the kidneys were utilized to determine the extent of influx of CD4(+) and CD8(+) cells and glomerular damage. Results. Dexamethasone induced a marked apoptosis of splenic CD4(+) and CD8 (+) cells, and it inhibited the production of anti-rabbit IgG and the influ x of CD8(+) cells and macrophages into the renal glomeruli. Crescent format ion and excretion of urinary proteins were also reduced. Galectin-9 failed to induce apoptosis in the CD4(+) cells; however, it induced apoptosis in t he CD8(+) cells and inhibited the infiltration of CD8(+) cells. Although ga lectin-1 and -3 did not induce the apoptosis in the T cells, they inhibited the accumulation of macrophages in the renal glomeruli. Like dexamethasone , the galectins also reduced the crescentic formation, proliferation of glo merular cells, and excretion of urinary proteins. Conclusions. Galectin-9 selectively induces apoptosis of the activated CD8( +) cells, while the macrophage influx into the kidney is modulated by all t hree galectins. This finding raises an interesting possibility for the util ity of galectins in the modulation of macrophages that are involved in immu ne-mediated glomerular diseases.