Nephrol Dial Transplant (2003) 18: 1072-1078
© 2003 European Renal Association-European Dialysis and Transplant Association
Increased production of chemotactic cytokines and elevated proliferation and expression of intercellular adhesion molecule-1 in rat mesangial cells treated with erythrogenic toxin type B and its precursor isolated from nephritogenic streptococci
1 Instituto de Investigaciones Clinicas ‘Dr. Americo Negrette’, Facultad de Medicina and 2 Instituto de Investigaciones de la Facultad de Odontologia, Facultad de Odontologia, Universidad del Zulia, Maracaibo, Venezuela
Background. Previous reports have demonstrated the presence of streptococcal erythrogenic toxin type B (ETB) as well as proliferation and expression of adhesion molecules along with leukocyte infiltrations in biopsies from patients with acute post-streptococcal glomerulonephritis (APSGN). The purpose of the present study was to correlate infiltrative and proliferative events with interactions between ETB or its precursor (ETBP) and intrinsic mesangial cells.
Methods. Rat mesangial cells were cultured with ETB or ETBP (50 µg/ml) while measuring production of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) and while examining proliferation and expression of intercellular adhesion molecule-1 (ICAM-1). After 24, 48 and 96 h of incubation, MCP-1 and MIP-2 in culture supernatants were assessed by enzyme-linked immunosorbent assay (ELISA). Cells were assessed for proliferation by incorporation of radioactive thymidine and expression of ICAM-1 was measured by indirect immunofluorescence and by cellular ELISA.
Results. Compared with controls, treatment with either ETBP or ETB significantly increased MCP-1 and MIP-2 levels in mesangial cell cultures. Mesangial cells also showed elevated proliferation at 96 h of culture when treated with streptococcal proteins. Although production of MCP-1 and MIP-2 was not correlated with proliferation, treatment with ETBP resulted in a significant correlation between MCP-1 production and proliferation. Immunofluorescence studies revealed an increased expression of ICAM-1 in ETBP/ETB-treated mesangial cells. In addition, cellular ELISA studies showed increased absorbance in cultures treated with ETBP/ETB. Finally, low serum concentrations in the culture medium potentiated the stimulatory effect of ETB on MCP-1 production.
Conclusions. Our findings, by demonstrating a role for cationic streptococcal ETB or ETBP in the induction of chemotactic molecules as well as the proliferation and expression of adhesion molecules, delineate an additional possible pathway for the pathogenesis of APSGN.
Keywords: erythrogenic toxin; glomerulonephritis; intercellular adhesion molecule-1; macrophage inflammatory protein-2; monocyte chemoattractant protein-1; proliferation
Correspondence and offprint requests to: Jesus A. Mosquera, MD, Apartado Postal 1151, Maracaibo 4001-A, Zulia, Venezuela. Email: mosquera99{at}hotmail.com
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