De‑O‑acylated lipooligosaccharide of E. coli B reduces the number of metastatic foci via downregulation of myeloid cell activity

Lipopolysaccharides are the main surface antigens and virulence factors of gramnegative bacteria. Removal of four esterbound fatty acid residues from hexaacyl lipid A of Escherichia coli lipooligosaccharide (LOS) resulted in the deOacylated derivative E. coli LOSOH (LOSOH). This procedure caused a significant reduction in the toxicity of this compound compared to the native molecule. We investigated the effect of such a structural LOS modification on its biological activity using in vitro assays with monocytic cells of the RAW264.7 line, dendritic cells of the JAWS II line, bone marrowderived dendritic cells (BMDCs), and spleen cells. Furthermore, in in vivo experiments with a melanoma B16 metastasis model, the antimetastatic activity of the compounds and spleen cell reactivity mediated by them representing a systemic response were analyzed. The results revealed that LOSOH demonstrated weaker ability than LOS to stimulate and polarize an immune response both in vitro and in vivo. It induced lower cytokine production by cells of myeloid lines. Multiple applications of LOSOH into mice injected intravenously with B16 cells significantly (P<0.05; P<0.01) reduced the number of metastatic foci in the lungs, presumably via silencing of myeloid cell reactivity as well as the inability to stimulate lymphoid cells both directly and indirectly. These findings suggest that LOSOH maintained in the body of metastasisbearing mice appears to modulate or downregulate the innate response, leading to the inability of blood myeloid cells to support the migration of melanoma cells to lung tissue.