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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3397-3405.
Prepublished online as a Blood First Edition Paper on July 18, 2006; DOI 10.1182/blood-2006-04-014779.


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IMMUNOBIOLOGY

Altered granulopoietic profile and exaggerated acute neutrophilic inflammation in mice with targeted deficiency in the sialyltransferase ST6Gal I

Mehrab Nasirikenari, Brahm H. Segal, Julie R. Ostberg, Ashlee Urbasic, and Joseph T. Lau

From the Departments of Molecular and Cellular Biology, Medicine, and Immunology, Roswell Park Cancer Institute, Buffalo, NY; and the Department of Pathobiology, University of Illinois at Urbana-Champaign.

Elevation of serum sialic acid and the ST6Gal-1 sialyltransferase is part of the hepatic system inflammatory response, but the contribution of ST6Gal-1 has remained unclear. Hepatic ST6Gal-1 elevation is mediated by P1, 1 of 6 promoters regulating the ST6Gal1 gene. We report that the P1-ablated mouse, Siat1{Delta}P1, and a globally ST6Gal-1–deficient mouse had significantly increased peritoneal leukocytosis after intraperitoneal challenge with thioglycollate. Exaggerated peritonitis was accompanied by only a modest increase in neutrophil viability, and transferred bone marrow–derived neutrophils from Siat1{Delta}P1 mice migrated to the peritonea of recipients with normal efficiency after thioglycollate challenge. Siat1{Delta}P1 mice exhibited 3-fold greater neutrophilia by thioglycollate, greater pools of epinephrine-releasable marginated neutrophils, greater sensitivity to G-CSF, elevated bone marrow CFU-G and proliferative-stage myeloid cells, and a more robust recovery from cyclophosphamide-induced myelosuppression. Bone marrow leukocytes from Siat1{Delta}P1 are indistinguishable from those of wild-type mice in {alpha}2,6-sialylation, as revealed by the Sambucus nigra lectin, and in the expression of total ST6Gal-1 mRNA. Together, our study demonstrated a role for ST6Gal-1, possibly from extramedullary sources (eg, produced in liver) in regulating inflammation, circulating neutrophil homeostasis, and replenishing granulocyte numbers.


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