NEURAMINIDASE PROMOTES NEUTROPHIL, LYMPHOCYTE AND MACROPHAGE INFILTRATION IN THE NORMAL RAT-KIDNEY

Neuraminidase (NA) is an enzyme produced by several microorganisms, wh ich is capable of liberating sialic acid from glycoproteins and modify ing cellular adhesion mechanisms. NA is considered a virulence factor in some bacterial species and has been implicated in the pathogenesis of acute poststreptococcal glomerulonephritis, a disease in which glom erular leukocyte infiltration is a prominent feature. We examined the effect of NA on kidney infiltration by neutrophils (PMN), T lymphocyte s (TL) and monocyte-macrophages (MM). Intravenous injection of NA resu lted in an early increase in the number of PMN (1 hr, 3.42 +/- 0.19 ce lls/cgs, mean +/- SEM; 3 hr, 3.63 +/- 0.13; 6 hr, 2.9 +/- 0.24; contro ls, 1.53 +/- 0.18; P < 0.001) and MM (1 hr, 3.49 +/- 0.16; 3 hr, 4.02 +/- 0.2; 6 hr, 3.88 +/- 0.27; controls 1.43 +/- 0.14; P < 0.001) in th e glomeruli, while TL increased later (24 hr, 2.29 +/- 0.14; 48 hr, 2. 4 +/- 0.2; 72 hr, 2.16 +/- 0.15; controls 0.7 +/- 0.07; P < 0.001). PM N and TL were also increased in the interstitium (up to ninefold for P MN and up to threefold for TL). Following i.v. injection of Cr-51-labe led NA-treated leukocytes, renal radioactive uptake was significantly increased al all times tested (percent radioactivity/gram of tissue af ter PMN injection, 3 hr, 5.57 +/- 0.46, mean +/- SEM; 12 hr, 5.38 +/- 0.77; 60 hr, 6.51 +/- 1.1; controls, 1.26 +/- 0.17, 1.75 +/- 0.25, and 2.46 +/- 0.08, respectively; P < 0.001 in each case. After TL injecti on, 3 hr, 3.21 +/- 0.58; 12 hr, 4.37 +/- 1.03; 60 hr, 4.11 +/- 0.65; c ontrols: 0.73 +/- 0.1, 1.53 +/- 0.29, and 1.18 +/- 0.12, respectively; P < 0.001 in each case. After MM injection, 3 hr, 1.39 +/- 0.16; 12 h r, 1.82 +/- 0.16; 60 hr, 2.33 +/- 0.3; controls, 0.87 +/- 0.1, 1.09 +/ - 0.11, and 1.04 +/- 0.24, respectively; P < 0.05 in each case). These results were not modified by prior splenectomy in the animal, or pre- treatment with desialized fetuin (to block binding of cells to possibl e lectin-like receptors) and polyethyleneimine or cationized ferritin (which bind to glomerular polianion). Our results indicate that NA ind uces binding of circulating cells to the kidneys, a finding that may b e relevant in the nephritogenicity associated with some NA-producing i nfections.