Sexual dimorphisms in the immune system of catechol-O-methyltransferase knockout mice.
The enzyme catechol-O-methyltransferase (COMT) is part of the metabolic pathway of 17β-estradiol, converting 2-hydroxyestradiol to 2-methoxyestradiol. We recently showed that administration of the COMT product 2-methoxyestradiol has anti-inflammatory and anti-osteoporotic effects. We have now investigated whether COMT affects the immune system, by immunologically phenotyping COMT deficient (COMT(-/-)) mice. Immunoglobulin production, T lymphocyte proliferation, NK cell cytotoxicity and oxygen radical production were assessed. In male COMT(-/-)-mice, the total number of T-, and B-lymphocytes from spleen increased but the T-cell proliferative response decreased. The NK cell population shifted toward less mature cells, leaving cytotoxic capacity unaffected. In COMT(-/-)-females, a higher frequency of neutrophils was found but the oxygen radical production was unaltered. In conclusion, only minor changes of the immune system were seen in COMT deficient mice, and the changes were usually seen in males. This study provides clues into how COMT activity, and hence gender differences, affects the immune system.
Centre for Bone and Arthritis Research (CBAR), Institute of Medicine Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. alexandra.stubelius@rheuma.gu.se
Alexandra
A
Stubelius
Anna S
AS
Wilhelmson
Joseph A
JA
Gogos
Asa
A
Tivesten
Ulrika
U
Islander
Hans
H
Carlsten
D000077584:2-Methoxyestradiol; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D005260:Female; D007107:Immune System / Q000166:cytology / Q000201:enzymology*; D007136:Immunoglobulins / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015394:Molecular Structure; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size; D012737:Sex Factors; D059010:Single-Cell Analysis; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology* / Q000378:metabolism; D014599:Uterus / Q000254:growth & development
D007136:Immunoglobulins; D004958:Estradiol; D000077584:2-Methoxyestradiol; C001390:2-hydroxyestradiol; D002394:Catechol O-Methyltransferase