Expression of natural cytotoxicity receptors on peritoneal fluid natural killer cell and cytokine production by peritoneal fluid natural killer cell in women with endometriosis.

PROBLEM: To investigate the relationship between the expression of natural cytotoxicity receptors (NCRs) on peritoneal fluid (PF) natural killer (NK) (pfNK) cells and cytokine production by pfNK cells in women with endometriosis. METHOD OF STUDY: Peritoneal fluid was collected from women with endometriosis undergoing laparoscopic surgery (n = 21) and controls without endometriosis (n = 28). The expression of NK cell surface antigens such as CD16 and NCRs (NKp46, NKp44 and NKp30) on pfNK cells, and cytokines production by pfNK cells [tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, GM-CSF and transforming growth factor (TGF)-ß1] were measured using multicolor flow cytometry. RESULTS: The percentages of CD56(+)/NKp46(+) cells and CD56(dim) /NKp46(+) cells in severe endometriosis group were significantly lower than that in controls. TNF-α and IFN-γ production by pfNK cells in severe endometriosis group was significantly higher than those in controls. CONCLUSION: The differential expression of NKp46, TNF-α, and IFN-γ on pfNK cells in women with severe endometriosis may allow the proliferation and angiogenesis of endometriotic cells.

Correlation between natural cytotoxicity receptors and intracellular cytokine expression of peripheral blood NK cells in women with recurrent pregnancy losses and implantation failures.

PROBLEM: Natural cytotoxicity receptors (NCRs) are unique markers, which regulate NK cell cytotoxicity and cytokine production. We investigated whether women with recurrent pregnancy losses (RPLs) and implantation failures have aberrant correlation between NCRs and intracellular cytokine expression of NK cells. METHOD OF STUDY: Peripheral blood NK cells (CD56(dim) and CD56(bright)) were analyzed for NCRs (NKp46, NKp44 and NKp30) and cytokine expression (TNF-alpha, IFN-gamma, IL-4, IL-10) using flow cytometry in RPL (n = 22), implantation failures (n = 23) or controls (n = 15). RESULTS: In type 1 cytokine studies, CD56(bright)/NKp30(+) cells in controls (r = 0.696, P < 0.05) were positively correlated with CD56(bright)/IFN-gamma(+)/TNF-alpha(+) cells. CD56(bright)/NKp46(+) cells in implantation failures (r = -0.76, P < 0.01) were negatively correlated with CD56(bright)/IFN-gamma(+)/TNF-alpha(-) cells. RPL did not have any correlation. In type 2 cytokine studies, CD56(+)/NKp46(+) cells (r = 0.758, P < 0.01) and CD56(+)/NKp30(+) cells (r = 0.637, P < 0.05) were positively correlated with CD56(bright)/IL-4(+)/IL-10(+) cells in controls. CD56(+)/NKp30(+) cells in implantation failures (r = -0.778, P < 0.05) were negatively correlated with CD56(bright)/IL-10(+)/IL-4(+) cells. There were no correlations in RPL. CONCLUSION: Recurrent pregnancy losses and implantation failures have lack of, or negative correlation between NCRs and intracellular cytokines expression. This observation suggests that excessive pro-inflammatory cytokine expression in NK cells in RPL and implantation failures may be exerted through the NCRs or interruption of signal transduction processes.