Modulation of NK cell lytic function by endometrial secretory factors: potential role in endometriosis.

Abstract

Development and progression of endometriosis have been suggested to be related to a defect of NK cells in the ability to eliminate endometrial fragments regurgitated with menstrual debris in ectopic sites. However, it has not been clarified yet whether the origin of this defect has to be attributed to an intrinsic alteration of NK cell population or to a consequence of the environmental system. The present study was designed to evaluate whether soluble factors of endometrial origin might directly interfere with NK cell lytic function. Media conditioned by 20 endometrial stromal cultures (10 from endometriosis patients and 10 from women without the disease) were examined to test their effects on NK cell-mediated cytotoxicity directed against endometrial stromal targets. NK cells were purified from peripheral blood samples by a two steps panning technique and incubated overnight with and without endometrial supernatants. Thereafter, the percentage of lysis against endometrial cells was detected in a 51Cr cytotoxicity assay. Media conditioned by the overall endometrial stromal cultures exerted a significant suppressive effect (P < 0.001) on NK cell function when compared to control NK fractions (mean percentage of cytotoxicity +/- SEM 17.46 +/- 2.8 and 29.41 +/- 1.49, respectively). No inhibitory effect was detect with conditioned media obtained from peritoneal cells and keratinocytes. Moreover, NK cell-mediated cytotoxicity resulted significantly more inhibited by the addition of endometrial supernatants obtained from endometriosis patients (mean percentage cytotoxicity +/- SEM 13.55 +/- 2.3, P < 0.05) when compared to those from women without the disease (mean percentage cytotoxicity +/- SEM 21.38 +/- 4.9). The results of this study indicate the existence of soluble non-specific factors(s) released by human endometrial cells able to interfere with NK cell killing. These factors could participate in the local regulation of the immunological mechanisms suggested to be involved in the development of endometriosis.