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

Mierzejewska,Jagoda; Szczygieł,Agnieszka; Anger‑Góra,Natalia; Rossowska,Joanna; Jarosz,Joanna; Wietrzyk,Joanna; Kaszowska,Marta; Maciejewska,Anna; Jachymek,Wojciech; Niedziela,Tomasz; Lukasiewicz,Jolanta; Lugowski,Czesław; Boratyński,Janusz; Pajtasz‑Piasecka,Elżbieta

doi:10.3892/or.2019.7403

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

Authors:
- Jagoda Mierzejewska
- Agnieszka Szczygieł
- Natalia Anger‑Góra
- Joanna Rossowska
- Joanna Jarosz
- Joanna Wietrzyk
- Marta Kaszowska
- Anna Maciejewska
- Wojciech Jachymek
- Tomasz Niedziela
- Jolanta Lukasiewicz
- Czesław Lugowski
- Janusz Boratyński
- Elżbieta Pajtasz‑Piasecka
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Affiliations: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53‑114 Wroclaw, Poland
Published online on: November 8, 2019 https://doi.org/10.3892/or.2019.7403
Pages: 270-281

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Abstract

Lipopolysaccharides are the main surface antigens and virulence factors of gram‑negative bacteria. Removal of four ester‑bound fatty acid residues from hexaacyl lipid A of Escherichia coli lipooligosaccharide (LOS) resulted in the de‑O‑acylated derivative E. coli LOS‑OH (LOS‑OH). 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 marrow‑derived dendritic cells (BM‑DCs), and spleen cells. Furthermore, in in vivo experiments with a melanoma B16 metastasis model, the anti‑metastatic activity of the compounds and spleen cell reactivity mediated by them representing a systemic response were analyzed. The results revealed that LOS‑OH 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 LOS‑OH 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 LOS‑OH maintained in the body of metastasis‑bearing 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.

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