INTERFERON-GAMMA (IFN-g) AND GRANULOCYTE-MACROPHAGE-COLONY STIMULATING FACTOR (GM-CSF) ENHANCE FORMATION OF MULTINUCLEATED GIANT CELLS DERIVED FROM MONOCYTES STIMULATED IN VITRO WITH Paracoccidioides brasiliensis ANTIGEN

NASCIMENTO M. P. P.(1), SOARES A. M. V. C.(2), NAKAIRA E. T.(1), PERAÇOLI M. T. S.(2).

(1)Departamento de Doenças Tropicais e Diagnóstico por Imagem, Faculdade de Medicina de Botucatu; (2)Departamento de Microbiologia e Imunologia, Instituto de Biociências, UNESP, Botucatu, SP, Brazil.

Cell fusion is a central phenomenon during the immune response that leads to multinucleated giant cells (MGC) formation. These cells are a common occurrence at sites of granulomatous inflammation and may be induced in vitro by stimulation with cytokines. This study investigated the effect of INF-g and GM-CSF on MGC formation in vitro from monocytes stimulated with P.brasiliensis antigen (PbAg). Peripheral blood monocytes obtained from healthy individuals were cultured for three days with or without stimulus such as: PbAg (100ug/mL) or PbAg plus IFN-g (50, 100 and 300 IU/mL), or PbAg plus GM-CSF (50, 100, 200, 500 and 1000 pg/mL). The fusion index (FI) and the percentage of MGC formation were determined after cell fixing and May-Grumwald-Giensa staining. The results demonstrated that monocyte incubation with PbAg or IFN-g or GM-CSF induces FI significantly higher than in control cultures without stimulus. Monocyte cultures stimulated with PbAg plus different GM-CSF concentrations showed FI significantly higher in comparison with cultures only stimulated with PbAg. The FI obtained in cultures stimulated with PbAg plus 300 UI INF-g were significantly higher than those observed in cultures only stimulated with PbAg or with different concentrations of INF-g. Together, these data suggest that IFN-g and GM-CSF play a positive modulatory  effect on MGC generation after monocyte stimulation with P.brasiliensis antigen.

KEY WORDS: Paracoccidioides brasiliensis, multinucleated giant cells, INF-g and GM-CSF

FINANCIAL SUPPORT: FAPESP no. 03/13743-0

CORRESPONDENCE TO:

Magda Paula Pereira do Nascimento, Departamento de Microbiologia e Imunologia do Instituto de Biociências, UNESP, Distrito de Rubião Júnior s/n, Botucatu, SP. Email: magdapaula@terra.com.br