Possible role of hematopoietic CD44/chondroitin sulfate interaction in extravasation of peripheral blood CD16(−) natural killer cells into human endometrium

Unique CD16(−) natural killer (NK) cells appear in the human cycling endometrium. Although their origin remains undetermined, one possible explanation is extravasation of circulating peripheral blood CD16(−) NK cells. Hematopoietic CD44 (CD44H) is an adhesion molecule expressed on leukocytes and plays a role in the initial step of leukocyte extravasation (leukocyte tethering/rolling). Recent studies have shown that CD44H binds to chondroitin sulfate (CS). To test the hypothesis that peripheral blood CD16(−) NK cells extravasate using the CD44H/CS interaction, we have compared the binding capacity of CD44H to immobilized CS among peripheral blood lymphocyte subsets, as well as determined the menstrual cycle-dependent expression of CD44H. Additionally, we have investigated the expression of the CS proteoglycan serglycin in human endometrial endothelial cells. CD44H expression on peripheral blood CD16(−) NK cells was higher compared with other lymphocyte subsets throughout the menstrual cycle. Peripheral blood CD16(−) NK cells bound preferentially to immobilized CS-A and CS-C compared with other lymphocyte subsets. The binding was significantly reduced by function-blocking anti-CD44H antibody. Serglycin expression in the human endometrial endothelial cells was greater in the secretory phase than in the proliferative phase. Progesterone (10−7 M to 10−8 M) significantly increased serglycin core protein expression in cultured human uterine microvascular endothelial cells, whereas 17β-estradiol had no effect. These results indicate that the interaction between CD44H on peripheral blood CD16(−) NK cells and CS on endometrial endothelial cells may play a role in extravasation of these NK cells into human endometrium. Serglycin may be a potential CS proteoglycan involved in this phenomenon.