Submitted April 3, 2006
Accepted July 3, 2006
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*
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, NY, USA
Departments of Medicine and Immunology, Roswell Park Cancer Institute, NY, USA
Department of Immunology, Roswell Park Cancer Institute, NY, USA
Department of Pathobiology, U. of Illinois, Urbana, IL, USA
* Corresponding author; email: joseph.lau{at}roswellpark.org.
Elevation of serum sialic acid and the ST6Gal-1 sialyltransferase are part of the hepatic systemic inflammatory response, but the contribution of ST6Gal-1 has remained unclear. ST6Gal-1 elevation is mediated by P1, one of six promoters regulating the ST6Gal-1 gene. We report that the P1-ablated mouse, Siat1
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 Siat1P1 mice migrated to the peritoneum of recipients with normal efficiency following thioglycollate challenge. Siat1P1 mice exhibited three-fold greater neutrophilia by thioglycollate, greater pool 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 cyclophosphoramide-induced myelosuppression. Bone marrow leukocytes from Siat1P1 are indistinguishable from wild-type mice in 
2,6-sialylation as revealed by the Sambucus nigra lectin, and in the expression of total ST6Gal-1 mRNA. Together, our study demonstrates a role for ST6Gal-1, possibly from extramedullary sources (e.g. that produced in liver), in regulating inflammation, circulating neutrophil homeostasis, and in replenishment of granulocyte numbers.
