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Innate immune defences in the human endometrium.

King AE, Critchley HO, Kelly RW - Reprod. Biol. Endocrinol. (2003)

Bottom Line: Such protection is critical to successful implantation and pregnancy.Secretory leukocyte protease inhibitor is expressed during the secretory phase of the cycle and has a range of possible roles including anti-protease and anti-microbial activity as well as having effects on epithelial cell growth.The sequential production of natural anti-microbial peptides by the endometrium throughout the menstrual cycle and at other sites in the female genital tract will offer protection from many pathogens, including those that are sexually transmitted.

View Article: PubMed Central - HTML - PubMed

Affiliation: MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Chancellor's Building, 49 Little France Crescent, Edinburgh, UK. a.king@hrsu.mrc.ac.uk

ABSTRACT
The human endometrium is an important site of innate immune defence, giving protection against uterine infection. Such protection is critical to successful implantation and pregnancy. Infection is a major cause of preterm birth and can also cause infertility and ectopic pregnancy. Natural anti-microbial peptides are key mediators of the innate immune system. These peptides, between them, have anti-bacterial, anti-fungal and anti-viral activity and are expressed at epithelial surfaces throughout the female genital tract. Two families of natural anti-microbials, the defensins and the whey acidic protein (WAP) motif proteins, appear to be prominent in endometrium. The human endometrial epithelium expresses beta-defensins 1-4 and the WAP motif protein, secretory leukocyte protease inhibitor. Each beta-defensin has a different expression profile in relation to the stage of the menstrual cycle, providing potential protection throughout the cycle. Secretory leukocyte protease inhibitor is expressed during the secretory phase of the cycle and has a range of possible roles including anti-protease and anti-microbial activity as well as having effects on epithelial cell growth. The leukocyte populations in the endometrium are also a source of anti-microbial production. Neutrophils are a particularly rich source of alpha-defensins, lactoferrin, lysozyme and the WAP motif protein, elafin. The presence of neutrophils during menstruation will enhance anti-microbial protection at a time when the epithelial barrier is disrupted. Several other anti-microbials including the natural killer cell product, granulysin, are likely to have a role in endometrium. The sequential production of natural anti-microbial peptides by the endometrium throughout the menstrual cycle and at other sites in the female genital tract will offer protection from many pathogens, including those that are sexually transmitted.

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Immunohistochemical localization of the WAP proteins, SLPI and elafin, in human endometrium. (A). SLPI immunolocalization in endometrium from the mid secretory phase. Immunoreactivity is present in the glandular epithelium and secretions. (B). Elafin immunolocalization in menstrual endometrium. Immunoreactivity is present in neutrophils infiltrating the endometrial stroma. Scale bars = 100 μm.
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Figure 2: Immunohistochemical localization of the WAP proteins, SLPI and elafin, in human endometrium. (A). SLPI immunolocalization in endometrium from the mid secretory phase. Immunoreactivity is present in the glandular epithelium and secretions. (B). Elafin immunolocalization in menstrual endometrium. Immunoreactivity is present in neutrophils infiltrating the endometrial stroma. Scale bars = 100 μm.

Mentions: The WAP protein, SLPI, has also been detected in the endometrial epithelium with peak expression in the mid-late secretory phase (Figure 2a) [39]. This protein may have important actions during the window of implantation. SLPI has several anti-inflammmatory actions including inhibition of the proinflammatory transcription factor, nuclear factor κB [40], and this combined with its anti-protease activity may prevent an excessive inflammatory response from occurring in the uterus at the time of implantation and during early pregnancy. In addition, SLPI has recently been suggested to have an effect on epithelial growth. Proepithelin (PEPI) is an epithelial growth factor that can be converted to a growth inhibitor, epithelin (EPI), by elastase. SLPI can form a complex with PEPI preventing its cleavage by elastase and hence, promote epithelial growth [41]. In vitro studies using the Ishikawa epithelial cell line (derived from an endometrial adenocarcinoma) have shown that SLPI can also increase expression of the cyclin D1 gene while inhibiting expression of anti-proliferative genes such as insulin-like growth factor binding protein-3 and lysyl oxidase [42]. The anti-microbial actions of SLPI are likely to be particularly important in the protection of the uterus from infection during implantation and early pregnancy. Indeed, it has been shown that the antibacterial activity of apical secretions from polarized endometrial epithelial cells can be reduced by incubation with an anti-SLPI antibody confirming that SLPI contributes to the antibacterial defences at the epithelial surface at least in vitro [43]. SLPI concentrations and the ratio of SLPI to elastase have also been found to increase in the peritoneal fluid of women suffering from endometriosis. Local peritoneal inflammation is one of the factors thought to be responsible for the symptoms of this disease and it has been suggested that SLPI concentrations are increased in response to this and that the anti-inflammatory and anti-protease actions of SLPI may limit the inflammatory process [44].


Innate immune defences in the human endometrium.

King AE, Critchley HO, Kelly RW - Reprod. Biol. Endocrinol. (2003)

Immunohistochemical localization of the WAP proteins, SLPI and elafin, in human endometrium. (A). SLPI immunolocalization in endometrium from the mid secretory phase. Immunoreactivity is present in the glandular epithelium and secretions. (B). Elafin immunolocalization in menstrual endometrium. Immunoreactivity is present in neutrophils infiltrating the endometrial stroma. Scale bars = 100 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC305332&req=5

Figure 2: Immunohistochemical localization of the WAP proteins, SLPI and elafin, in human endometrium. (A). SLPI immunolocalization in endometrium from the mid secretory phase. Immunoreactivity is present in the glandular epithelium and secretions. (B). Elafin immunolocalization in menstrual endometrium. Immunoreactivity is present in neutrophils infiltrating the endometrial stroma. Scale bars = 100 μm.
Mentions: The WAP protein, SLPI, has also been detected in the endometrial epithelium with peak expression in the mid-late secretory phase (Figure 2a) [39]. This protein may have important actions during the window of implantation. SLPI has several anti-inflammmatory actions including inhibition of the proinflammatory transcription factor, nuclear factor κB [40], and this combined with its anti-protease activity may prevent an excessive inflammatory response from occurring in the uterus at the time of implantation and during early pregnancy. In addition, SLPI has recently been suggested to have an effect on epithelial growth. Proepithelin (PEPI) is an epithelial growth factor that can be converted to a growth inhibitor, epithelin (EPI), by elastase. SLPI can form a complex with PEPI preventing its cleavage by elastase and hence, promote epithelial growth [41]. In vitro studies using the Ishikawa epithelial cell line (derived from an endometrial adenocarcinoma) have shown that SLPI can also increase expression of the cyclin D1 gene while inhibiting expression of anti-proliferative genes such as insulin-like growth factor binding protein-3 and lysyl oxidase [42]. The anti-microbial actions of SLPI are likely to be particularly important in the protection of the uterus from infection during implantation and early pregnancy. Indeed, it has been shown that the antibacterial activity of apical secretions from polarized endometrial epithelial cells can be reduced by incubation with an anti-SLPI antibody confirming that SLPI contributes to the antibacterial defences at the epithelial surface at least in vitro [43]. SLPI concentrations and the ratio of SLPI to elastase have also been found to increase in the peritoneal fluid of women suffering from endometriosis. Local peritoneal inflammation is one of the factors thought to be responsible for the symptoms of this disease and it has been suggested that SLPI concentrations are increased in response to this and that the anti-inflammatory and anti-protease actions of SLPI may limit the inflammatory process [44].

Bottom Line: Such protection is critical to successful implantation and pregnancy.Secretory leukocyte protease inhibitor is expressed during the secretory phase of the cycle and has a range of possible roles including anti-protease and anti-microbial activity as well as having effects on epithelial cell growth.The sequential production of natural anti-microbial peptides by the endometrium throughout the menstrual cycle and at other sites in the female genital tract will offer protection from many pathogens, including those that are sexually transmitted.

View Article: PubMed Central - HTML - PubMed

Affiliation: MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Chancellor's Building, 49 Little France Crescent, Edinburgh, UK. a.king@hrsu.mrc.ac.uk

ABSTRACT
The human endometrium is an important site of innate immune defence, giving protection against uterine infection. Such protection is critical to successful implantation and pregnancy. Infection is a major cause of preterm birth and can also cause infertility and ectopic pregnancy. Natural anti-microbial peptides are key mediators of the innate immune system. These peptides, between them, have anti-bacterial, anti-fungal and anti-viral activity and are expressed at epithelial surfaces throughout the female genital tract. Two families of natural anti-microbials, the defensins and the whey acidic protein (WAP) motif proteins, appear to be prominent in endometrium. The human endometrial epithelium expresses beta-defensins 1-4 and the WAP motif protein, secretory leukocyte protease inhibitor. Each beta-defensin has a different expression profile in relation to the stage of the menstrual cycle, providing potential protection throughout the cycle. Secretory leukocyte protease inhibitor is expressed during the secretory phase of the cycle and has a range of possible roles including anti-protease and anti-microbial activity as well as having effects on epithelial cell growth. The leukocyte populations in the endometrium are also a source of anti-microbial production. Neutrophils are a particularly rich source of alpha-defensins, lactoferrin, lysozyme and the WAP motif protein, elafin. The presence of neutrophils during menstruation will enhance anti-microbial protection at a time when the epithelial barrier is disrupted. Several other anti-microbials including the natural killer cell product, granulysin, are likely to have a role in endometrium. The sequential production of natural anti-microbial peptides by the endometrium throughout the menstrual cycle and at other sites in the female genital tract will offer protection from many pathogens, including those that are sexually transmitted.

Show MeSH
Related in: MedlinePlus