Neuraminidase promotes neutrophil, lymphocyte and macrophage infiltration in the normal rat kidney

Neuraminidase promotes neutrophil, lymphocyte and macrophage infiltration in the normal rat kidney. Neuraminidase (NA) is an enzyme produced by several microorganisms, which is capable of liberating sialic acid from glycoproteins and modifying 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 glomerular leukocyte infiltration is a prominent feature. We examined the effect of NA on kidney infiltration by neutrophils (PMN), T lymphocytes (TL) and monocyte-macrophages (MM). Intravenous injection of NA resulted in an early increase in the number of PMN (1 hr, 3.42 ± 0.19 cells/cgs, mean ± SEM; 3 hr, 3.63 ± 0.13; 6 hr, 2.9 ± 0.24; controls, 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 the 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). PMN and TL were also increased in the interstitium (up to ninefold for PMN and up to threefold for TL). Following i.v. injection of 51Cr-labeled NA-treated leukocytes, renal radioactive uptake was significantly increased at all times tested (percent radioactivity/gram of tissue after 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 injection, 3 hr, 3.21 ± 0.58; 12 hr, 4.37 ± 1.03; 60 hr, 4.11 ± 0.65; controls: 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 hr, 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 possible lectin-like receptors) and polyethyleneimine or cationized ferritin (which bind to glomerular polianion). Our results indicate that NA induces binding of circulating cells to the kidneys, a finding that may be relevant in the nephritogenicity associated with some NA-producing infections