Effect of leukocyte depletion on glomerular dynamics during acute glomerular immune injury

Large doses of anti-glomerular basement membrane antibody (AGBM-Ab) have been shown consistently to decrease both single nephron filtration rate (SNGFR) and the glomerular ultrafiltration coefficient (LpA) within 60 min of administration of the antibody. Both the decrease in SNGFR and LpA may be the result of infiltration of leukocytes blocking capillary loops and/or endothelial cell separation from the glomerular basement membrane through leukocyte dependent activated cytotoxic products or by mechanisms associated with leukocyte activation and infiltration. Administration of 2.5 micrograms/g body wt AGBM-Ab was performed in 10 control Munich-Wistar rats and in six Munich-Wistar rats in which 3 to 5 days prior to micropuncture experiments the rats were splenectomized and then irradiated to produce leukocyte depletion. Micropuncture measurements were performed in a condition of plasma volume expansion both prior to and after AGBM-Ab administration. In the control group, SNGFR decreased from 64 +/- 3 to 48 +/- 2 nl/min X g kidney wt after AGBM-Ab administration due to a decrease in LpA from 0.13 to 0.06 nl X sec-1 X mm Hg-1 X g kidney wt-1. This decrease in either SNGFR or LpA did not occur in the leukocyte depleted group. Linear deposits of IgG and C3 were similar in both groups. Polymorphonuclear leukocytes were significantly decreased in glomerulus from 7.4 +/- 0.7 in control vs. 0.7 +/- 0.3 in leukocyte depletion (P less than 0.01). There was no difference in glomerular dynamics between controls and leukocyte depleted rats prior to AGBM-Ab administration.(ABSTRACT TRUNCATED AT 250 WORDS)