Expression of macrophage inflammatory protein-1beta in human endometrium: its role in endometrial recruitment of natural killer cells

J Clin Endocrinol Metab. 2003 Apr;88(4):1809-14. doi: 10.1210/jc.2002-020980.


Human endometrium is infiltrated by natural killer (NK) cells throughout the menstrual cycle. The number of endometrial NK cells is low in the proliferative phase, but acutely increases after ovulation, and reaches a peak in the late secretory phase, suggesting that endometrium recruits these leukocytes selectively from circulating peripheral blood. We investigated the expression of macrophage inflammatory protein (MIP)-1beta, a potential chemoattractant for NK cells, in the endometrium. RT-PCR and ELISA revealed that MIP-1beta is expressed in the endometrium throughout the menstrual cycle at both the message and protein levels. MIP-1beta expression is stronger in the secretory phase endometrium than in the proliferative phase endometrium. Immunohistochemistry revealed that MIP-1beta is localized in the surface epithelial cells, glandular epithelial cells, and perivascular stromal cells throughout the menstrual cycle. Stromal cells in a wider perivascular area became immunoreactive in the secretory phase. There was a strong correlation between the endometrial MIP-1beta concentration and the number of endometrial NK cells. Progesterone significantly induced MIP-1beta secretion from cultured endometrial stromal cells, whereas 17beta-estradiol had a weak effect. These results suggest that endometrial MIP-1beta may be involved in the recruitment of NK cells from circulating peripheral blood.

MeSH terms

  • Adult
  • Cells, Cultured
  • Chemokine CCL4
  • Culture Media, Conditioned
  • Endometrium / chemistry*
  • Endometrium / cytology
  • Endometrium / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Estradiol / pharmacology
  • Female
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Killer Cells, Natural / physiology*
  • Lymphocyte Count
  • Macrophage Inflammatory Proteins / analysis
  • Macrophage Inflammatory Proteins / genetics*
  • Macrophage Inflammatory Proteins / physiology*
  • Menstrual Cycle
  • Middle Aged
  • Ovulation
  • Progesterone / pharmacology
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / metabolism


  • Chemokine CCL4
  • Culture Media, Conditioned
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Progesterone
  • Estradiol