Induction of murine spiral artery modification by recombinant human interferon-gamma.
Functions of uterine natural killer (uNK) cells during mouse pregnancy are maintenance of decidua basalis and promotion of uterine spiral artery modification, a process that results in thin-walled, dilated, elongated arteries with lowered resistance. Murine models indicate spiral artery modifications are triggered by release of the cytokine interferon (IFN)-gamma from uNK cells. The purpose of this study was to determine if human IFN-gamma could induce structural changes in the unmodified spiral arteries found in pregnant, alymphoid (uNK-, NK-, T-, B-) mice. Spiral arteries in pregnant Rag2 null/common cytokine chain (c) gamma null mice were modified, in a dose response manner, by daily injections of rhIFN-gamma. Administration of low dose LPS did not induce morphologically recognized structural changes. These findings are key in building humanized murine models of pregnancy since they suggest Rag2 null/gammac null mice provide a bioassay system that would detect the functioning of human uNK cells under in vivo conditions.
Monk
J M
JM
Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
Leonard
S
S
McBey
B A
BA
Croy
B A
BA
D000818:Animals; D001158:Arteries / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000172:deficiency; D004305:Dose-Response Relationship, Drug; D005260:Female; D006651:Histocytochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011247:Pregnancy; D011994:Recombinant Proteins; D014599:Uterus / Q000098:blood supply*
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; C499308:Rag2 protein, mouse; D011994:Recombinant Proteins; D007371:Interferon-gamma