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(Journal of Leukocyte Biology. 2002;72:93-100.)
© 2002 by Society for Leukocyte Biology

Decrease in cAMP levels modulates adhesion to fibronectin and immunostimulatory ability of human dendritic cells

Dalia Burzyn^*, Carolina C. Jancic^*, Sandra Zittermann^*, María I. Keller Sarmiento, Leonardo Fainboim^*, Ruth E. Rosenstein and H. Eduardo Chuluyan^*

^* Laboratorio de Inmunogenética, Hospital de Clínicas "José de San Martín", and
Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Argentina

Correspondence: Dr. H. Eduardo Chuluyan, Laboratorio de Inmunogenética, Piso 3, Sala 4, Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Avenida Córdoba 2351 (C.P. 1120), Buenos Aires, Argentina. E-mail: chulu{at}interar.com.ar

The aim of the present study was to analyze the early events elicited by tumor necrosis factor (TNF-) on monocyte-derived dendritic cells (moDC) adhesion to fibronectin (FN) and the involvement of cAMP in the signal transduction mechanism. The intracellular concentration of cAMP and moDC adhesion to FN decreased after TNF- treatment. An inverted dose-dependency for TNF- effect was observed for adhesion and cAMP levels. The presence of a phosphodiesterase (PDE) inhibitor (IBMX) and cAMP analogs (8Br-cAMP, Db-cAMP) reversed the observed TNF- effects. The role of cAMP was analyzed further by examining the cAMP levels in nonadhered and adhered, TNF--treated moDC. Nonadhered moDC showed lower cAMP levels compared with adhered moDC. Furthermore, nonadhered moDC showed higher IL-12 content and allostimulatory ability compared with adhered moDC. The higher allostimulatory capacity was abolished in the presence of cAMP analogs and a PDE inhibitor. These results suggest that cAMP levels correlate with TNF--induced changes of moDC adhesion and allostimulatory capacity.

Key Words: IL-12 • signal transduction • second messengers

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