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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, NF\u03baB 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 NF\u03baB 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.<\/jats:p>","DOI":"10.1093\/glycob\/cwac032","type":"journal-article","created":{"date-parts":[[2022,6,5]],"date-time":"2022-06-05T16:39:29Z","timestamp":1654447169000},"page":"701-711","source":"Crossref","is-referenced-by-count":15,"title":["Extracellular ST6GAL1 regulates monocyte\u2013macrophage development and survival"],"prefix":"10.1093","volume":"32","author":[{"given":"Michael E","family":"Rusiniak","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center , Elm and Carlton Streets, Buffalo, NY 14263, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick R","family":"Punch","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center , Elm and Carlton Streets, Buffalo, NY 14263, United States"},{"name":"Department of Oral Biology, University at Buffalo , Buffalo, NY 14215, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitai C","family":"Hait","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center , Elm and Carlton Streets, Buffalo, NY 14263, United States"},{"name":"Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center , Elm and Carlton Streets, Buffalo, NY 14263, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Maiti","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center , Elm and Carlton Streets, Buffalo, NY 14263, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T","family":"Burns","sequence":"additional","affiliation":[{"name":"Translational Glycomics Center, Blood Research Institute , 8727 W. Watertown Plank Rd, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Digantkumar","family":"Chapla","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia , Athens, GA 30602, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley W","family":"Moremen","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia , Athens, GA 30602, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia , Athens, GA 30602, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4956-5363","authenticated-orcid":false,"given":"Lance","family":"Wells","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia , Athens, GA 30602, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Hoffmeister","sequence":"additional","affiliation":[{"name":"Translational Glycomics Center, Blood Research Institute , 8727 W. 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