ALPHA- 2 -M/LRP1 INDUCES DIFFERENTIAL MACROPHAGE MIGRATION IN NORMOXIC AND HYPOXIC CONDITIONS

FERRER D; JALDIN-FINCATI JAVIER; SÁNCHEZ MC; CHIABRANDO GUSTAVO

Potrero de los Funes, San Luis

Congreso; 2011, XLVII Reunión Anual / 2011, 47th Annual Meeting; 2011

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Alpha2-Macroglobulin (2M) is a proteinase inhibitor, which is recognized by LDL receptor-related protein 1 (LRP1). Previously, we demonstrated that 2M/LRP1 system induces intracellular signaling activation, MMP-9 expression and cellular migration in Raw264.7 macrophage-derived cell lines. It is known that tissue macrophages play several inflammatory functions under hypoxic conditions. Hypoxia is an inductor of LRP1 gene expression in tumoral cells. However, the hypoxic effect on the LRP1 expression and cell migration in macrophages has not been established. Herein we investigated the 2M effect on the Raw264.7 cell migration under cell cultured conditions of normoxia (O : 21%) and hypoxia 2 (O : 1.5%) using wound-healing assays. In addition, we have 2 examined the LRP1 gene and protein expression in Raw264.7 cells using RT-PCR and Western blot. We observed that 2M induced an increased cellular motility of RAW 264.7 cells in hypoxia compared to normoxia. Under hypoxia, LRP1 presented an increased mRNA and protein level compared to these cells cultured under normoxia. In conclusion, our data demonstrate that 2M promotes an increased cell migration of macrophages under hypoxia, which together with the hypoxia-induced LRP1 expression may be significant in the macrophage activity during inflammatory processes.