Abstract 17

Background. An imbalance between MMPs and TIMPs, which can be modulated by antiinflammatory drugs, may contribute to neonatal lung injury. Aims. To study in a model of human monocytic cell line (HL-60), constitutively expressing MMPs, the effects of GTP depletion on differentiation, proliferation and apoptosis. Methods. Differentiation (FACS on CD11b, superoxide gener.), proliferation (BrdU incorp.), apoptosis (tunel reaction), and GTP levels (HPLC), were studied in growing HL-60 cells (5-10×104 cells/ml), with Mycophenolic acid (MPA, 0-10 mM), a specific IMP-dehydrogenase inhibitor, and with guanosine (G, 50 mM), which reverses MPA effects by increasing GTP. Results. MPA induced a time- dose-dependent inhibition of proliferation and a drop of GTP. MPA > 2 µM and incubation > 48 h induced apoptosis. Lower MPA levels increased both differentiation indices. The effects of MPA were reversed by Guanosine. Conclusions. Low levels of GTP induce cell differentiation, associated with MMPs production. The effects of drugs on MMPs and TIMPs production through the GPT dependent pathway could be studied in this HL-60 cell model. (Supported by a Grant of the Italian Ministry of Health)