Extracellular ST6GAL1 regulates monocyte-macrophage development and survival.

Abstract

Interaction of immune cells with the systemic environment is necessary for the coordinated development and execution of immune responses. Monocyte-macrophage lineage cells reside at the junction of innate and adaptive immunity. Previously we reported that the sialyltransferase ST6GAL1 in the extracellular milieu modulates B cell development and IgG production, granulocyte production, and attenuates acute airway inflammation to bacterial challenge in mouse models. Here, we report that extracellular ST6GAL1 also elicits profound responses in monocyte-macrophage lineage cells. We show that recombinant ST6GAL1 adheres to subsets of thioglycolate-elicited inflammatory cells in the mouse peritoneum and to cultured human monocyte THP-1 cells. Exposure of the inflammatory cells to recombinant ST6GAL1 elicited wholesale changes in the gene expression profile of primary mouse myeloid cells; most notable was the striking up-regulation of monocyte-macrophage and monocyte-derived dendritic cell development pathway signature genes and transcription factors PU.1, NFκB and their target genes, driving increased monocyte-macrophage population and survival ex vivo. In the cultured human monocyte cells, the essential cell surface receptor of the monocyte-macrophage lineage, the M-CSF receptor (M-CSF-R, Csfr1) was a target of extracellular ST6GAL1 catalytic activity. Extracellular ST6GAL1 activated the M-CSF-R and initiated intracellular signaling events, namely, the nuclear translocation of NFκB subunit p65, and phosphorylation of ERK 1/2 and AKT. The findings implicate extracellular ST6GAL1 in monocyte development by a mechanism initiated at the cell surface and support an emerging paradigm of an extracellular glycan-modifying enzyme as a central regulator coordinating immune hematopoietic cell development and function.

• Authors: Michael E Rusiniak, Patrick R Punch, Nitai C Hait, Aparna Maiti, Robert T Burns, Digantkumar Chapla, Kelley W Moremen, Peng Zhao, Lance Wells, Karin Hoffmeister, Joseph T Y Lau
• Journal: Glycobiology (Glycobiology) Vol. 32 Issue 8 Pg. 701-711 (07 13 2022) ISSN: 1460-2423 [Electronic] England
• PMID: 35661210 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antigens, CD
• Macrophage Colony-Stimulating Factor
• Sialyltransferases
• ST6GAL1 protein, human

Topics

• Animals
• Antigens, CD (metabolism)
• Cell Differentiation
• Humans
• Macrophage Colony-Stimulating Factor (metabolism)
• Macrophages (metabolism)
• Mice
• Monocytes (metabolism)
• Phosphorylation
• Sialyltransferases (genetics, metabolism)
• Signal Transduction
• THP-1 Cells