title: GM-CSF and TNF-alpha synergize to increase in vitro granuloma size of PBMC from humans induced by Schistosoma mansoni recombinant 28-kDa GST.
abstract: The 28-kDa Glutathione S-transferase of Schistosoma mansoni (Sm28 GST) was described as a protective antigen capable of reducing female fecundity and the number of eggs in mice hepatic tissues. The role of GM-CSF and TNF-alpha in the in vitro granuloma reaction of peripheral blood mononuclear cells (PBMC) from chronic intestinal schistosomiasis patients before and after chemotherapy treatment to S. mansoni recombinant Sm28 GST was evaluated. Treatment of PBMC with recombinant Sm28 GST caused a significant increase in granuloma formation when compared to SEA or SWAP. Contrary to SEA or SWAP, Sm28 GST was not capable of inducing significant cellular proliferation. Moreover, recombinant Sm28 GST promoted a significant elevation in GM-CSF and TNF-alpha levels. However, we did not detect any significant IL-10 production. When Sm28 GST was applied in the presence of anti-GM-CSF or anti-TNF-alpha antibodies in cultures, we observed a significant decrease in granuloma size. Indeed, our results demonstrated that Sm28 GST was capable of promoting high in vitro granuloma index, and this event was associated with the balance of GM-CSF and TNF-alpha. These evidences suggest a role for GM-CSF as a major mediator in increasing granuloma reaction in human schistosomiasis. This event may contribute to exacerbate the pathology resulting from egg deposition in host tissues.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Caixa Postal 486, CEP 32 270-901, Belo Horizonte, MG, Brazil.
authors.forename: Cíntia M F
authors.initials: CM
authors.lastname: Rezende
authors.forename: Tércio S
authors.initials: TS
authors.lastname: Goes
authors.forename: Vinícius S
authors.initials: VS
authors.lastname: Goes
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
authors.forename: M F
authors.initials: MF
authors.lastname: Leite
authors.forename: Alfredo M
authors.initials: AM
authors.lastname: Goes
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005982:Glutathione Transferase / Q000378:metabolism / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006099:Granuloma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000201:enzymology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005982:Glutathione Transferase