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Published online before print July 15, 2008

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(Journal of Leukocyte Biology. 2008;84:1065-1074.)
© 2008 by Society for Leukocyte Biology

CD56^bright cells increase expression of 4 integrin at ovulation in fertile cycles

Crystal G. Peralta^*, Victor K. Han^*,, Julie Horrocks, B. Anne Croy and Marianne J. van den Heuvel^,1

Departments of
^* Anatomy and Cell Biology and
Pediatrics, University of Western Ontario, London, Ontario, Canada;
Mathematics and Statistics, University of Guelph, Guelph, Ontario, Canada; and
Anatomy and Cell Biology, Queens University, Kingston, Ontario, Canada

¹ Corresopndence: Department of Pediatrics, University of Western Ontario, 4910 Line 36, R R 5, Stratford, ON, Canada N5A 6S6. E-mail: mheuvel{at}quadro.net

Leukocyte content of human endometrium changes rapidly after ovulation, particularly as a result of gains in CD56^bright uterine NK (uNK) cells. We have proposed that uNK precursor cells are found within the blood CD56^bright pool and are recruited to decidualizing endometrium through functional changes in their adhesion molecules and chemokine receptors. This study sought to quantify alterations in adhesion molecules, cytokines, chemokines, and receptors induced in circulating CD56⁺ cells of fertile and infertile women by ovulation. Blood was drawn from 12 fertile volunteers and six female-infertility patients at Menstrual Cycle Day (d) 5 and on the day following the preovulatory surge of luteinizing hormone (LH). CD56^bright, CD56^dim, and CD56⁺CD3⁺ cell subsets were isolated and evaluated by flow cytometry, quantitative PCR, or Western blotting. In CD56^bright cells from fertile but not infertile women, ₄ integrin increased between d5 and the preovulatory LH surge. CD56^dim and NKT cells did not show a change in ₄ integrin but differed significantly between fertile and infertile donors, and infertile donors had reduced homing molecule expression in CD56^dim and NKT cells, and at ovulation, their NKT cells showed elevated cytokine production. None of the circulating CD56⁺ cell subsets had transcripts for receptors for estrogen, progesterone, LH, or prolactin. Thus, immunological events associated with the LH surge induce alterations in all subsets of CD56⁺ cells, and the unique induction of ₄ integrin in CD56^bright cells of fertile women constitutes a potential method to promote uterine homing.

Key Words: human • NK cells • adhesion molecules • chemokine receptors • reproductive immunology