The Mucin MUC16 (CA125) Binds to NK Cells and Monocytes from Peripheral Blood of Women with Healthy Pregnancy and Preeclampsia

Abstract

Problem MUC16 (CA125) released from ovarian tumors binds to NK cells and monocytes via the inhibitory receptor Siglec-9. Here, we investigate if MUC16 also binds to circulating immune cells during pregnancy and in women with preeclampsia. Method of study MUC16 binding was monitored by flow cytometry and immunoprecipitation and RT-PCR was used to monitor indigenous expression in immune cells. Serum CA125 levels were measured by a clinical assay. Results MUC16 was equally distributed on Siglec-9pos CD16pos/CD56dim and CD16neg/CD56br NK cells in the healthy pregnant and preeclampsia groups. While serum CA125 levels and number of NK and monocytes were similar, increased binding of MUC16 was observed on these immune cells in the preeclampsia cohort as compared to the healthy pregnant samples. Conclusion MUC16 binding to NK cells and monocytes likely contributes to tolerance of the fetal allograft from maternal responses and may also serve as a novel biomarker for preeclampsia.

Endogenous airway mucins carry glycans that bind Siglec-F and induce eosinophil apoptosis

“…49-52 MUC2 glycans reportedly can bind to CD33 (Siglec-3) on monocytes and dendritic cells and induce apoptosis 53 , while glycans on MUC16 are recognized by NK cells and monocytes via Siglec-9. 54, 55 In comparison to the work reported here, the glycan structures carried by these other siglec-binding mucins remain poorly characterized and none were derived from lung. While the currently and previously reported studies support an emerging theme, namely the functional importance of mucin-siglec interactions, the tissue- and cell-type specific regulation of mucin glycosylation must be considered carefully in defining functionally relevant siglec ligands.…”

MUC16: molecular analysis and its functional implications in benign and malignant conditions

“…This interaction may contribute toward suppression of maternal immune response toward fetal tissue. Also, an increased binding was detected in the preeclampsia cohort as compared to pregnant women (13). Hence, shed MUC16 when bound to siglec‐9 could serve as an indicator for the onset of preeclampsia in pregnant women.…”

“…On investigating the functional role of MUC16, it was also observed that enhanced shedding of MUC16 from the uterodome might occur, as soluble MUC16 has been detected in the cervical mucus and sera of women having a normal cycle (94). Interestingly, Tyler et al (13) have shown that shed MUC16 can bind to immune cells (NK cells and monocytes) that were isolated from pregnant women and patients with preeclampsia (mediated via siglec‐9 interaction). This interaction may contribute toward suppression of maternal immune response toward fetal tissue.…”

Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

“…Consistent with this notion, Muc1 null mice display greatly enhanced placental resorption (Croy et al 1997 ). In addition, MUC16 binds to NK cells of pregnant women, presumably mediated by Siglec-9 on NK cells (Belisle et al 2010 ;Tyler et al 2012 ). With regard to trophoblast invasion, overexpression of MUC1 and Siglec-6 are associated with preeclampsia (Shyu et al 2011 ); however, trophoblast TMs have not been formally demonstrated to carry Siglec-6 ligands.…”