Erythrogenic toxin type B and its precursor isolated from nephritogenic streptococci induce leukocyte infiltration in normal rat kidneys

Background. Leukocyte infiltration is a common feature in renal biopsies fr om patients with acute poststreptococcal glomerulonephritis (APSGN). Cation ic streptococcal erythrogenic toxin type B (ETB) and its precursor (ETBP) h ave been implicated in the pathogenesis of the disease, and the presence of ETB has been evidenced in renal biopsies from patients with APSGN. The pre sent studies were performed to determine the effect of the ETBP and ETB on renal leukocyte infiltration and the mechanism(s) implicated in the phenome non. Methods. Male Sprague-Dawley rats were injected intrarenally with 100 mu g of ETB or ETBP. Animals were sacrificed at 1, 6 and 24 h after injection an d renal samples were studied by indirect immunofluorescence for the presenc e of leukocyte common antigen (LCA(+)) cells, C3, monocyte chemotactic prot ein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1), and by direct immunofluorescence for the presence of immunoglobulins. ETB and ETBP were tested for chemotactic effect and migration inhibition factor (MIF) activit y by chemotaxis under agarose and agarose microdroplet methods, respectivel y. Streptococcal proteins were also tested for the capacity to induce MIF a ctivity in rat glomerular cultures. To test for the influence of cationic c harge on renal LCA(+) cell infiltration, rats were injected with cationized ferritin or polyethyleneimine (PEI) and sacrificed 1 h later. Results. An increased number of LCA(+) cells was found in glomeruli and int erstitial areas in ETB- or ETBP-injected animals. ETB and ETBP showed chemo tactic and MIF activity on neutrophils and macrophages, and ETBP induced MI F activity in supernatants of glomerular cultures. Data obtained from C3, M CP-1, ICAM-1 or immunoglobulin renal staining in experimental animals were not significantly different when compared to control values. Cationized com pounds failed to induce LCA(+) cell infiltration; however, an increased num ber of glomerular LCA(+) cells was observed after PEI perfusion. Conclusions. ETB and ETBP induce renal LCA(+) cell infiltration during a sh ort period after intrarenal injection, and this finding could be mediated b y chemotactic and MIF activities. These observations could be relevant in t he early events of pathogenesis of APSGN.