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

Abstract

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, Siat1DeltaP1, 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 Siat1DeltaP1 mice migrated to the peritonea of recipients with normal efficiency after thioglycollate challenge. Siat1DeltaP1 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 Siat1DeltaP1 are indistinguishable from those of wild-type mice in alpha2,6-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.

• Authors: Mehrab Nasirikenari, Brahm H Segal, Julie R Ostberg, Ashlee Urbasic, Joseph T Lau
• Journal: Blood (Blood) Vol. 108 Issue 10 Pg. 3397-405 (Nov 15 2006) ISSN: 0006-4971 [Print] United States
• PMID: 16849643 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Sialyltransferases
• beta-D-Galactoside alpha 2-6-Sialyltransferase

Topics

• Acute Disease
• Animals
• Bone Marrow Transplantation
• Cell Survival
• Granulocytes (physiology)
• Inflammation (enzymology, etiology)
• Leukocytosis
• Leukopoiesis (physiology)
• Mice
• Mice, Knockout
• Neutrophils (pathology, physiology)
• Peritonitis
• Sialyltransferases (deficiency, physiology)
• beta-D-Galactoside alpha 2-6-Sialyltransferase