Apoptosis of human endometrium mediated by perforin and granzyme B of NK cells and cytotoxic T lymphocytes.
Endometrial stromal granulocytes (EGs) were found to be a major component of human endometrial stroma in the late secretory phase. However, the role of EGs in the mechanism of human endometrial menstruation has not been clarified. Immunohistochemistry of CD56, perforin, granzyme B, and vimentin, in situ detection of apoptosis by TUNEL (TdT-mediated dUTP-biotin nick and labeling) and electron microscopy were performed in endometrial tissue samples with normal menstrual cycles. We analyzed the number of immunostained cells in the functional layer of stroma and the number of apoptotic cells detected by TUNEL in the endometrial glandular cells. Double-staining revealed that CD56-positive endometrial stromal cells were simultaneously positive for both perforin and granzyme B, and negative for vimentin, which recognized stromal tissue. Vimentin was positive for the predecidual cells and negative for EGs. CD56-positive EGs involving perforin and granzyme B were progressively recruited during the secretory phases before menstruation. Apoptosis in endometrial glandular cells increased from the late secretory phase, which maximized at the menstrual period. This finding suggests that the cytotoxic granules released from EGs, which are derived from cytotoxic T lymphocytes and natural killer cells, are initiators of the apoptotic pathway that induces endometrial menstruation.
Konno
R
R
Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan. konno@ob-gy.med.tohoku.ac.jp
Igarashi
T
T
Okamoto
S
S
Sato
S
S
Moriya
T
T
Sasano
H
H
Yajima
A
A
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D019002:CD56 Antigen / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000502:physiology*; D005260:Female; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007694:Killer Cells, Natural / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D008598:Menstruation / Q000502:physiology; D008854:Microscopy, Electron; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012016:Reference Values; D012697:Serine Endopeptidases / Q000378:metabolism / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
D019002:CD56 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014746:Vimentin; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases