Dysfunction of monocytes and dendritic cells in patients with premature ovarian failure.
OBJECTIVE
Due to the presence of ovarian antibodies it has been suggested that premature ovarian failure (POF) belongs to the autoimmune endocrinopathies. Monocytes and the monocyte-derived dendritic cells play a prominent role in the initial stages of endocrine autoimmune reactions: the accumulation of monocytes/dendritic cells and the clustering of dendritic cells in endocrine organs is one of the first phenomena of an autoimmune endocrinopathy.


METHODS
This report describes a study on (1) the chemotactic responsiveness of blood monocytes, and (2) the cluster capability of blood dendritic cells in POF patients. The monocyte chemotaxis was determined using the cell's capability to polarize (changes in shape determined by light microscopy) under the influence of the chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (fMLP). The cluster capability of dendritic cells was tested by allowing the dendritic cells to form aggregates with allogenic lymphocytes in vitro.


RESULTS
The blood monocytes of 46% of a total of 28 POF patients showed a decreased fMLP induced monocyte polarization in comparison to healthy control values. None of the young female controls (N = 28) and postmenopausal women (N = 17), showed such a defective monocyte polarization. The blood dendritic cells of 36% of the POF patients showed a decreased cluster capability. Defects in monocyte polarization and dendritic cell clustering were not affected by therapies aimed at changes in the estrogen levels or gonadotropin levels of the patients [using estrogen substitution therapy, gonadotropin-releasing hormone (GnRH) analog, follicle-stimulating hormone (FSH)].


CONCLUSIONS
A redistribution of active monocytes and of active dendritic cells from the peripheral blood to the ovaries may be the cause of the described abnormalities. Since similar abnormalities in monocyte function and dendritic cell function have been described in Graves' disease and type I diabetes, the data strengthen the view that POF is one of the endocrine autoimmune diseases.
Hoek
A
A
Department of Obstetrics and Gynaecology, Free University Hospital, Rotterdam, The Netherlands.
van Kasteren
Y
Y
de Haan-Meulman
M
M
Schoemaker
J
J
Drexhage
H A
HA
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D048429:Cell Size / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004311:Double-Blind Method; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006728:Hormones / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008593:Menopause / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D016649:Primary Ovarian Insufficiency / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism
D004967:Estrogens; D006728:Hormones; D007987:Gonadotropin-Releasing Hormone; D009240:N-Formylmethionine Leucyl-Phenylalanine