Altered granulopoietic profile and exaggerated acute neutrophilic inflammation in mice with targeted deficiency in the sialyltransferase ST6Gal I.
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.
Nasirikenari
Mehrab
M
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Segal
Brahm H
BH
Ostberg
Julie R
JR
Urbasic
Ashlee
A
Lau
Joseph T
JT
D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D006098:Granulocytes / Q000502:physiology*; D007249:Inflammation / Q000201:enzymology / Q000209:etiology*; D007964:Leukocytosis; D019891:Leukopoiesis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology* / Q000502:physiology; D010538:Peritonitis; D012799:Sialyltransferases / Q000172:deficiency / Q000502:physiology*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase