Regulation of natural-killer cell cytotoxicity and enhancement of complement factors in the spontaneously aborted mouse placenta.
OBJECTIVE
To evaluate the cytotoxicity of uterine natural killer (NK) cells and identify major biological factors fluctuating in the spontaneously aborted placenta.


METHODS
Spontaneously aborted placentae were examined by using histology, molecular biology, and DNA microarray analysis.


METHODS
Laboratories and animal center at a medical college.


METHODS
C57BL/6 mice.


METHODS
None.


METHODS
Up-regulation of the inhibitory system of uterine NK cells and enhancement of complement factors in aborted placenta.


RESULTS
In uteri on day 14 of pregnancy, 9.69% +/- 11.6% (+/-SD) implantation sites spontaneously aborted. Labyrinthine trophoblasts at abortion sites had nuclei that were positive for DNA fragment detection, as well as apoptotic morphology. Many uterine NK cells were present at abortion sites, but cytotoxic factors such as perforin, granzyme B, and Fas-Fas ligand were expressed at very low levels. In contrast, the expression level of Ly49 NK-cell receptors, which mediate an inhibitory signal for cytotoxicity, was enhanced at abortion sites. Deoxyribonucleic acid microarray analysis showed that adipsin, an activating enzyme for complement component C3, was strongly enhanced in aborted placenta, and positive reactions for adipsin and C3 were confirmed by immunohistochemistry.


CONCLUSIONS
In the process of spontaneous abortion, the cytotoxicity of uterine NK cells is inhibited, and the innate immune system through adipsin and complement C3 appears to be influential.
Kusakabe
Ken
K
Department of Anatomy and Cell Biology, Division of Basic Medicine I, Osaka Medical College, Osaka, Japan.
Naka
Mayumi
M
Ito
Yuko
Y
Eid
Nabil
N
Otsuki
Yoshinori
Y
D000022:Abortion, Spontaneous / Q000276:immunology*; D000818:Animals; D003176:Complement C3 / Q000276:immunology*; D011416:Complement Factor D / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy; D014599:Uterus / Q000276:immunology
D003176:Complement C3; D011416:Complement Factor D