- Research
- Open Access
Intercellular adhesion molecule-1 expression in human endometrium: implications for long term progestin only contraception
https://doi.org/10.1186/1477-7827-4-2
© Schatz et al; licensee BioMed Central Ltd. 2006
- Received: 28 June 2005
- Accepted: 30 January 2006
- Published: 30 January 2006
Abstract
Background
Neutrophils infiltrate the endometrium pre-menstrually and after long-term progestin only-contraceptive (LTPOC) treatment. Trafficking of neutrophils involves endothelial cell-expressed intercellular adhesion molecule (ICAM-1). Previous studies observed that ICAM-1 was immunolocalized to the endothelium of endometrial specimens across the menstrual cycle, but disagreed as to whether extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies across the menstrual cycle.
Methods
Endometrial biopsies were obtained from women across the menstrual cycle and from those on LTPOC treatment (either Mirena or Norplant). The biopsies were formalin-fixed and paraffin-embedded with subsequent immunohistochemical staining for ICAM-1.
Results
The current study found prominent ICAM-1 staining in the endometrial endothelium that was of equivalent intensity in different blood vessel types irrespective of the steroidal or inflammatory endometrial milieu across the menstrual cycle and during LTPOC therapy. Unlike the endothelial cells, the glands were negative and the stromal cells were weakly positive for ICAM immunostaining.
Conclusion
The results of the current study suggest that altered expression of ICAM-1 by endothelial cells does not account for the influx of neutrophils into the premenstrual and LTPOC-derived endometrium. Such neutrophil infiltration may depend on altered expression of neutrophil chemoattractants.
Keywords
- Menstrual Cycle
- Abnormal Uterine Bleeding
- Menstrual Phase
- Norplant
- Mirena
Background
The premenstrual human endometrium displays increased prostaglandin-generating capacity, elevated levels of inflammatory cytokines [1, 2] and a leukocyte infiltrate that comprises nearly one-half of the cell population [3–5]. Among endometrial leukocyte subtypes, neutrophils are virtually absent until the mid-luteal phase, but comprise a significant portion of the leukocytes in the menstrual phase. During long-term progestin-only contraceptive (LTPOC) administration, the endometrium also experiences enhanced prostaglandin-generating capacity and increased inflammatory cytokine levels [6, 7]. Administration of Norplant, which releases levonorgestrel (LNG) from subdermal rods, and Mirena, which releases LNG from an intrauterine system, leads to endometrial infiltration of matrix metalloproteinase-9 (MMP-9) positive neutrophils [8], and macrophages [9], respectively.
Endothelial cell-expressed cellular adhesion molecules mediate leukocyte trafficking [10]. In this regard, particular attention has been directed at the physiological and pathological roles played by intercellular adhesion molecule (ICAM-1), a 76-114-kDa surface glycoprotein that has five extracellular immunoglobulin-like domains [11–14].Transmigration of leukocytes involves high-affinity binding of LFA-1 or Mac-1 on their surface to ICAM-1 expressed on the endothelium [10]. ICAM-1 deficient mice experience numerous inflammatory response abnormalities including impaired neutrophil trafficking [15, 16]. Although ICAM-1 has been immunolocalized to the endothelium of various blood vessel types in specimens of cycling endometrium, there are conflicting reports as to whether extra-endothelial cell types also express ICAM-1, and whether ICAM-1 expression varies across the menstrual cycle [17–19]. In view of this lack of consensus, the current study reassessed immunohistochemical (IHC) staining for ICAM-1 in endometrial biopsies across the menstrual cycle, and extended the use of IHC staining of ICAM-1 to include endometrial tissues exposed to subdermal (Norplant) and intra-uterine (Mirena, Schering) exogenous progestogens. Both LTPOC types provide safe and effective contraception for several years. Norplant is particularly well suited for use in underdeveloped countries where access to trained medical personnel is limited. They are discontinued primarily because of inflammation-associated abnormal uterine bleeding (AUB) as a source of personal annoyance and discomfort as well as cultural and religious taboo [20, 21]. The levonorgestrel-releasing intra-uterine system (LNG-IUS, Mirena) is now increasingly used as an effective contraceptive and for its associated health benefits, including reduction in menstrual blood loss [22].
Prior to menstruation and during progestin-only contraception (Norplant, Mirena), secretion of MMPs by endometrial leukocytes as well as cytokines that can act as autocrine/paracrine modulators of MMP expression [5], are thought to enhance degradation of the vascular support structure leading to stromal collapse and bleeding [23–26]. The current study sought to determine whether altered expression of ICAM-1 could account for infiltration of neutrophils into the menstrual and LTPOC-derived endometrium.
Methods
Tissues
After receiving written informed consent and approval from the Institutional Research Board (IRB) of New York University Medical Center and Bellevue Hospital, specimens of endometrium were obtained across the menstrual cycle (four each from the follicular and luteal phases and five from the menstrual phase) from hysterectomies for benign conditions (e.g. myomas without abnormal uterine bleeding), and histologically dated by the criteria of Noyes et al [27]. For studies on LTPOC-derived endometrium, institutional ethical review and approval was obtained from the New York University IRB and the Lothian Research Ethical Committee, Scotland and written informed consent was obtained for biopsy collection.
The subjects had regular menstrual cycles and had not used hormonal or intrauterine contraception in the six months prior to insertion of Norplant or Mirena. Patients did not exhibit symptoms characteristic of endometriosis such as pelvic pain, dysmennorhea, dysparunia, or infertility. The only way to confirm a diagnosis of endometriosis is through exploratory surgery. Such surgery would be prompted by symptoms that would have ruled out the use of those patients for our study. For the cycling endometrium patients were pre-menopausal between 32 and 43 years of age who were not receiving any hormonal treatments. For the LTPOC endometrium patients were premenopausal, between 28 and 45 years of age, had regular menstrual cycles and had not used any hormonal or intrauterine contraception in the six months prior to receiving the LTPOC treatment.
Norplant specimens
Prior to insertion of Norplant biopsies were collected from four women (two in the follicular and two in the luteal phase) by Pipelle suction curette (Laboratoire CCD, Paris, France). Only patients who experienced bleeding while on the Norplant treatment were used. Biopsies were collected using an operative hysteroscope connected to a video camera to facilitate separate sampling of bleeding and non-bleeding sites as previously described [25]. These samples were taken after 3 and 12 months post Norplant insertion.
Mirena specimens
Endometrial biopsies were also obtained from four women (two in the follicular and two in the luteal phase) prior to and at 1, 3, 6, and 12 months after intrauterine insertion of the LNG-intrauterine system by Pipelle suction biopsy.
Immunohistochemistry (IHC)
Specimens of endometrium obtained across the menstrual cycle as well as from control, and levonorgestrel treated (Norplant, Mirena) subjects were fixed in 4% paraformaldehyde and embedded in paraffin. Four μm sections (4 μm) were deparaffinized, rehydrated and washed in Tris-buffered saline [TBS: 20 mmol/l Tris-HCl, 150 mmol/l NaCl (pH 7.6)], which was used for all washes and for dilution of the antibody. Antigen retrieval was carried-out by incubating sections in sodium citrate buffer (10 mM, pH 6.0) in a microwave oven at 750 Watts for 5 minutes. The sections were then rinsed in 3% hydrogen peroxide to block endogenous peroxidase and incubated for 1 hour at room temperature with either of the following primary antibodies: a goat polycolonal ICAM-1 (CD54) antibody from R&D Systems (R&D Systems, Inc., Minneapolis, MN) or a monoclonal antibody against the Platelet Adhesion Molecule (PECAM) (CD31) from Dako (DakoCytomation California, Inc., Carpinteria, CA). Staining was visualized using the avidin-biotin peroxidase complex (Vectastain ABC kit, Vector Laboratories, Burlingame, CA) and the 3,3'-diaminobenzidine tetrahydrochloride (Sigma-Aldrich, St. Louis, MI) chromogen substrate. Light hematoxylin stain was used for nuclear counterstaining. Negative controls for each tissue section consisted of substituting the corresponding pre-immune serum for the primary antibody.
Assessment of immunohistochemical (IHC) staining and statistical analysis
Intensity of ICAM-1 staining was evaluated using a semi-quantitative 4-point rating method with the following scoring system: 0, absence of staining; 1, light staining; 2 moderate staining; and 3, strong staining. Each of these possible scores was established in advance of rating the fields via reference to external stained specimens unrelated to this study. In order to determine inter-rater reliability of this scale, two independent judges scored a series of 35 separate fields on slides from 4 separate patient samples. The degree of concordance was then assessed by use of Cohen's kappa statistic, which yielded a value of 0.67, indicating a high degree of agreement between the judges.
Non-parametric statistical analysis was performed by the Mann-Whitney Rank Sum Test with p < 0.05 considered significant.
Results
Immunostaining for ICAM-1 and CD 31 in human endometrium during the menstrual cycle. Negative control for menstrual endometrium (A). Prominent ICAM-1 staining is evident in the endothelium in endometrial specimens from the follicular phase (C), luteal phase (D), and menstrual phase (E, F). Similar endothelial cell staining intensity and specificity for CD 31 is seen in the menstrual specimen shown in (B). The prominent structure in the menstrual specimen shown in (F) is a "stromal ball," which results from degenerative changes of the stroma. Note the compressed blood vessels displaying prominent immunostaining for ICAM-1, whereas the surrounding stromal cells were only weakly positive. Arrow = blood vessel; g = gland. Bar = 50 μm.
Immunostaining for ICAM-1 in human endometrium during long term only contraceptive (LTPOC) administration. IHC staining in the endothelium was prominent and specific for the endothelium in in all endometrial specimens examined. Samples obtained from women using Norplant (subdermal LNG) (B-E)-: (B) 3 months post-Norplant non-bleeding site; (C) 3 months post-Norplant, bleeding site; (D) 12 months post-Norplant, non-bleeding site; and (E) 12 months post Norplant, bleeding site. Similar results were seen in endometrial specimens from women using Mirena (intrauterine LNG) (F-I):-;(F) 3 months post-Mirena, non-bleeding (F); 3 months post-Mirena, bleeding; (G) 12 months post-Mirena, non-bleeding; and (I) 12 months post-Mirena, bleeding. Note that the stromal cells exhibit a much greater decidualization reaction following intrauterine administration of LNG (F-I) than after subdermal LNG (B-E). Arrow = blood vessel; g = gland; DC = decidualized stromal cell. Bar = 50 μm.
Discussion
The current study found that human endometrial endothelial cells displayed prominent IHC staining for ICAM-1 in specimens obtained from the follicular, luteal and menstrual phases, and after administration of the LTPOCs, Norplant (subdermal LNG) and Mirena (intrauterine LNG) and that this staining was of equivalent intensity in all vessels examined. By contrast, the glands exhibited virtually no immunostaining and the stromal cells only weak immunoreactivity. Although IHC staining for ICAM-1 was previously demonstrated in the endometrial endothelium of specimens obtained across the menstrual cycle [17–19], two of the reports found significant ICAM-1 staining in the stromal cells [18, 19], with one study noting that ICAM-1 levels in both stromal cells and endothelial cells were elevated in menstrual endometrium compared with specimens examined earlier in the menstrual cycle [18].
The demonstration in the current study that ICAM-1 levels are equivalent in the endometrial endothelium of specimens from the E2-dominated follicular phase, the progesterone-exposed luteal phase, and the steroid-withdrawal-initiated menstrual phase suggests that ICAM-1 expression is not under direct ovarian steroid regulation. This conclusion was supported by the ICAM-1 immunostaining results obtained in endometrial biopsies during use of subdermal and intrauterine LNG (Norplant and Mirena respectively) contraception. That both LTPOCs produce a hyperprogestational endometrial milieu is suggested by the observation of significantly high endometrial levels of the progesterone receptor (PR) isoforms PRA and PRB after administration of Norplant [24] as well as the injectable LTPOC, Provera [23], whereas PRA appears to mediate the long-term effects of LNG in the endometrium during intrauterine LNG contraception [6]. Endometrial levels of LNG that are 1000 times greater with intrauterine delivery (Mirena) than with subdermal LNG administration (Norplant) [28]. However, the current study observed no difference in endometrial endothelial ICAM-1 immunostaining regardless of which LNG formulation was evaluated.
Evidence presented in the current study also argues against a role for the local inflammatory milieu in regulating endothelial cell expressed ICAM-1. Thus, equivalent immunostaining intensity was observed when follicular and luteal phase endometria were compared with menstrual, Norplant, and Mirena-derived endometria, which undergo a marked leukocyte infiltration [3–5, 8, 9] and exhibit other local pro-inflammatory changes such as a high prostaglandin-generating capacity and elevated interleukin-8 (IL-8) levels [1, 2, 6, 7].
ICAM-1 is both constitutively expressed and transcriptionally regulated on the surface of several cell types [29]. Consistent with the latter, the ICAM-1 gene promoter contains several cis-acting elements that predict responsiveness to pro-inflammatory cytokines and reactive oxygen species (ROS). Cooperativity between transcription factors C/EBP and NfκB mediate tumor necrosis factor alpha (TNF-α) and interleukin 1beta (IL-1β) responses. Actions of H2O2 are mediated by antioxidant response elements (ARE), which bind transcription factors AP-1 and Ets [29]. As expected, TNF-α, whose pro-inflammatory activity requires ROS formation, induces ICAM-1 expression in endothelial and epithelial cells and H2O2 induces ICAM-1 expression in endothelial cells. However, H2O2 does not affect ICAM-1 expression in epithelial cells [30].
Previously reported ICAM-1 immunostaining in non-pregnant and gestational endometrium. FT: first trimester; FF-PE: formalin-fixed, paraffin-embedded; PE: pre-eclampsia, IUGR: intrauterine growth retardation
Reference | Tissue type | Tissue Preparation | Endothelial CellICAM-1 staining | Non-endothelial CellICAM-1 staining |
---|---|---|---|---|
17 | Cycling endometrium | Frozen (formalin-fix) | Strong, constitutive | Uniform staining of glands, stroma, and epithelium; strong lymphoid staining |
18 | Cycling endometrium | Frozen (formalin-fix) | Strong but variable among vessel types with peak at menstrual | Glandular and luminal epithelium negative, stroma weak in proliferative/secretory phases but strong at menstrual |
19 | Cycling endometrium | Frozen (acetone-fix) and FF-PE | Strong throughout entire cycle | Glandular and luminal epithelium variable, stroma stained throughout cycle with increase expression in menstrual; widespread lymphoid staining |
31 | FT Decidua | Frozen (acetone-fix) | Strong in all vessel types | Glands negative, stroma weak, moderate staining of lymphocytes |
32 | FT Decidua, placenta | Frozen (acetone-fix) | Strong in all vessel types | Stroma negative, strong lymphocyte staining, strong staining of decidua parietalis |
33 | FT decidua | Frozen (acetone-fix) | Strong in all vessel types | Glands negative, some stroma positive |
34 | Decidua, placental bed | Frozen (acetone-fix) | Strong, unchanged in normal vs. PE, IUGR, or PE+IUGR | Weak scattered stromal cell staining |
35 | Decidua, placenta | Frozen (acetone-fix) | Strong, unchanged in normal vs. PE | Villous trophoblasts negative, <10% interstitial trophoblasts stained |
36 | FT decidua | FF-PE | Strong in all vessel types, same in normal vs. inflammation; constitutive | Glands negative, stroma weak |
Regulation of neutrophil migration into inflammatory sites reflects interactions between the IL-8 chemokine and the ICAM-1 adhesion molecule. The former establishes a chemotactic gradient that promotes neutrophil trafficking from the circulation towards the endothelium [39]. This enables the latter to mediate neutrophil rolling and adhesion prior to transendothelial migration [40]. Neutrophils are rich source of gelatinase B (MMP-9) [41], which degrades basement membrane associated collagens IV and V [42]. Moreover, neutrophil-derived MMP-9 cleaves IL-8 to a truncated form [IL-8(7-77)] with 10–30- fold greater potency in promoting neutrophil activation and chemotaxis [41]. The onset of AUB during LTPOC administration stems from fragile, abnormally distended vessels with impaired basement membranes"[43, 44]. Administration of LTPOCs produces local hypoxia stemming from reduced uterine vasomotion (45), and increases stromal cell expression of tissue factor, which can generate thrombin at local sites of AUB [46]. The demonstration in the current study that ICAM-1 is constitutively expressed by the endometrial endothelium highlights the important role that altered IL-8 expression plays in regulating neutrophil trafficking into the endometrium. Toward that end, we recently demonstrated that IL-8 expression is enhanced by hypoxia and thrombin in stromal cells derived from pre-decidualized human endometrium [47].
Conclusion
In the context of our current observations, constitutive endothelial ICAM-1 expression alone cannot account for the marked neutrophil infiltration that characterizes both premenstrual human endometrium as well as the endometrium resulting from LTPOC therapy.
Declarations
Acknowledgements
This work was supported by a grant from the National Institutes of Health 5 RO1 HD033937-06 (CJL).
Authors’ Affiliations
References
- Critchley HO, Jones RL, Lea RG, Drudy TA, Kelly RW, Williams AR, Baird DT: Role of inflammatory mediators in human endometrium during progesterone withdrawal and early pregnancy. J Clin Endocrinol Metab. 1999, 84 (1): 240-248. 10.1210/jc.84.1.240.PubMedGoogle Scholar
- Baird DT, Cameron ST, Critchley HOD, Drudy TA, Howe A, Jones RL, Lea RG, Kelly RW: Prostaglandins and menstruation. Eur J Obstet Gynecol Rep Biol. 1996, 7: 15-17. 10.1016/S0301-2115(96)02568-7.View ArticleGoogle Scholar
- Starkey PM, Clover LM, Rees MCP: Variation during the menstrual cycle of immune cell populations in human endometrium. Eur J Obstet Gynecol Reprod Biol. 1991, 39: 203-207. 10.1016/0028-2243(91)90058-S.View ArticlePubMedGoogle Scholar
- Bulmer JN, Morrison L, Longfellow M, Ritson A, Pace D: Granulated lymphocytes in human endometrium: histochemical and immunohistochemical studies. Hum Repro. 1991, 6: 791-798.Google Scholar
- Salamonsen LA, Wooley DE: Menstruation: induction by matrix metalloproteinases and inflammatory cells. J of Repro Immunol. 1999, 44: 1-27. 10.1016/S0165-0378(99)00002-9.View ArticleGoogle Scholar
- Critchley HOD, Wang H, Kelly RW, Gebbie AE, Glasier AF: Progestin receptor isoforms and prostaglandin dehydrogenase in the endometrium of women using a levonorgesterel-releasing intra-uterine system. Hum Reprod. 1998, 3: 11210-1217.Google Scholar
- Jones RL, Critchley HO: Morphological and functional changes in human endometrium following intrauterine levonorgestrel delivery. Hum Reprod. 2000, 15 (Suppl 3): 162-172.View ArticlePubMedGoogle Scholar
- Vincent AJ, Malakooti N, Zhang J, Rogers PA, Affandi B, Salamonsen LA: Endometrial breakdown in women using Norplant is associated with migratory cells expressing matrix metaloproteinase-9 (gelatinase B). Hum Reprod. 1999, 14: 807-815. 10.1093/humrep/14.3.807.View ArticlePubMedGoogle Scholar
- Critchley HO, Wang H, Jones RL, Kelly RW, Drudy TA, Gebbie AE, Buckley CH, McNeilly AS, Glasier AF: Morphological and functional features of endometrial decidualization following long-term intrauterine levonorgestrel delivery. Hum Reprod. 1998, 13 (5): 1218-1224. 10.1093/humrep/13.5.1218.View ArticlePubMedGoogle Scholar
- Springer TA: Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994, 76: 301-314. 10.1016/0092-8674(94)90337-9.View ArticlePubMedGoogle Scholar
- Wang Q, Doerschuk CM: The signaling pathways induced by neutrophil-endothelial cell adhesion. Antioxid Redox Signal. 2002, 4 (1): 39-47. 10.1089/152308602753625843.View ArticlePubMedGoogle Scholar
- Greenwood J, Etienne-Manneville S, Adamson P, Couraud PO: Lymphocyte migration into the central nervous system: implication of ICAM-1 signaling at the blood-brain barrier. Vascul Pharmacol. 2002, 38 (6): 315-322. 10.1016/S1537-1891(02)00199-4.View ArticlePubMedGoogle Scholar
- Nishibori M, Takahashi HK, Mori S: The regulation of ICAM-1 and LFA-1 interaction by autacoids and statins: a novel strategy for controlling inflammation and immune responses. J Pharmacol Sci. 2003, 92 (1): 7-12. 10.1254/jphs.92.7.View ArticlePubMedGoogle Scholar
- Ren G, Dewald O, Frangogiannis NG: Inflammatory mechanisms in myocardial infarction. Curr Drug Targets Inflamm Allergy. 2003, 2 (3): 242-256. 10.2174/1568010033484098.View ArticlePubMedGoogle Scholar
- Hayflick JS, Kilgannon P, Gallatin WM: The intercellular adhesion molecule (ICAM) family of proteins. New members and novel functions. Immunol Res. 1998, 17 (3): 313-327. ReviewView ArticlePubMedGoogle Scholar
- Sligh \surJE Jr, Ballantyne CM, Rich SS, Hawkins HK, Smith CW, Bradley A, Beaudet AL: Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1993, 90 (18): 8529-8533.PubMed CentralView ArticlePubMedGoogle Scholar
- Tabibzadeh SS, Poubourdis D: Expression of leukocyte adhesion molecules in human endometrium. Amer J Clin Pathol. 1990, 93: 183-189.Google Scholar
- Tawia SA, Beaton LA, Rogers PAW: Immunolocalization of the cellular adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and platelet adhsion molecule (PECAM), in human endometrium throughout the menstrual cycle. Hum Reprod. 1993, 8: 175-181.View ArticlePubMedGoogle Scholar
- Thomson AJ, Greer MR, Young A, Boswell F, Telfer JF, Cameron IT, Norman JE, Campbell S: Expression of intercellular adhesion molecules ICAM-1 and ICAM-2 in human endometrium throughout the menstrual cycle. Mol Hum Reprod. 1999, 5 (1): 64-70. 10.1093/molehr/5.1.64.View ArticlePubMedGoogle Scholar
- Shulnan LP, Nelson AL, Darney PD: Recent developments in hormone delivery systems. Am J Obstet Gynecol. 2004, 190 (4 Suppl): S39-48. 10.1016/j.ajog.2004.01.064.View ArticleGoogle Scholar
- McGavigan CJ, Cameron I: The Mirena levonorgestrel system. Drugs Today (Barc). 2003, 39 (12): 973-984. 10.1358/dot.2003.39.12.799415.View ArticleGoogle Scholar
- Critchley HO: Endometrial effects of progestogens. Gyn Forum. 2003, 8: 6-10.Google Scholar
- Hickey M, Simbar M, Markham R, Young L, Manconi F, Russell P, Fraser IS: Changes in vascular basement membrane in the endometrium of Norplant users. Hum Reprod. 1999, 14 (3): 716-721. 10.1093/humrep/14.3.716.View ArticlePubMedGoogle Scholar
- Lockwood CJ, Runic R, Wan L, Demopoulos R, Schatz F: The role of tissue factor in regulating endometrial hemostasis: implications for progestin-only contraception. Hum Reprod. 2000, 15: 144-151.View ArticlePubMedGoogle Scholar
- Runic R, Schatz F, Wan L, Demopoulos R, Krikun G, Lockwood CJ: Effects of norplant on endometrial tissue factor expression and blood vessel structure. J Clin Endocrinol Metab. 2000, 85: 3853-3859. 10.1210/jc.85.10.3853.PubMedGoogle Scholar
- Rogers PA: Endometrial vasculature in Norplant users. Hum Reprod. 1996, 11 (Suppl 2): 45-50.View ArticlePubMedGoogle Scholar
- Noyes RW, Hertig AT, Rock J: Dating the endometrial biopsy. Fertil Steril. 1950, 1: 3-25.Google Scholar
- Pekonen F, Nyman T, Lahteenmaki P, Haukkamaa M, Rutanen EM: Intrauterine progestin induces continuous insulin-like growth factor- binding protein-1 production in the human endometrium. J Clin Endocrinol Metab. 1992, 75: 660-664. 10.1210/jc.75.2.660.PubMedGoogle Scholar
- Roebuck KA, Finnegan A: Regulation of intercellular adhesion molecule-1 (CD54) gene expression. (Review). J Leukoc Biol. 1999, 66 (6): 876-888.PubMedGoogle Scholar
- Roebuck KA: Oxidative stress regulation of IL-8 and ICAM-1 gene expression:differential activation and binding of the transcription factors AP-1 and NF kappa B. (Review). Int J Mol Med. 1999, 3: 223-230.Google Scholar
- Marzusch K, Ruck P, Geiselhart A, Handgretinger R, Dietl JA, Kaiserling E, Horny HP, Vince G, Redman CW: Distribution of cell adhesion molecules on CD56++, CD3-, CD16- large granular lymphocytes and endothelial cells in first-trimester human decidua. Hum Reprod. 1993, 8 (8): 1203-1208.PubMedGoogle Scholar
- Burrows TD, King A, Loke YW: Expression of adhesion molecules by endovascular trophoblast and decidual endothelial cells: implications for vascular invasion during implantation. Placenta. 1994, 15 (1): 21-33.View ArticlePubMedGoogle Scholar
- Ruck P, Marzusch K, Kaiserling E, Horny HP, Dietl J, Geiselhart A, Handgretinger R, Redman CW: Distribution of cell adhesion molecules in decidua of early human pregnancy. An immunohistochemical study. Lab Invest. 1994, 71 (1): 94-101.PubMedGoogle Scholar
- Lyall F, Greer IA, Boswell F, Young A, Macara LM, Jeffers MD: Expression of cell adhesion molecules in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth retardation. Placenta. 1995, 16 (7): 579-587. 10.1016/0143-4004(95)90027-6.View ArticlePubMedGoogle Scholar
- Jaakkola K, Jokimaa V, Kallajoki M, Jalkanen S, Ekholm E: Pre-eclampsia does not change the adhesion molecule status in the placental bed. Placenta. 2000, 21 (2–3): 133-141. 10.1053/plac.1999.0460.View ArticlePubMedGoogle Scholar
- Lockwood CJ, Paidas M, Krikun G, Koopman LA, Masch R, Kuczynski E, Kliman H, Baergen RN, Schatz F: Inflammatory cytokine and thrombin regulation of interleukin-8 and intercellular adhesion molecule-1 expression in first trimester human decidua. J Clin Endocrinol Metab. 2005, 90 (8): 4710-4715. 10.1210/jc.2004-2528.View ArticlePubMedGoogle Scholar
- Lockwood CJ, Matta P, Krikun G, Koopman LA, Masch R, Toti P, Arcuri F, Huang ST-J, Funai EF, Schatz F: Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor alpha and interleukin 1 beta in first trimester human decidual cells: implications for preeclampsia. Am J Pathol.Google Scholar
- Reister F, Frank HG, Kingdom JC, Heyl W, Kaufmann P, Rath W, Huppertz B: Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women. Lab Invest. 2001, 81 (8): 1143-1152.View ArticlePubMedGoogle Scholar
- Springer TA: Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994, 76: 301-314. 10.1016/0092-8674(94)90337-9.View ArticlePubMedGoogle Scholar
- Issekutz AC, Rowter D, Springer TA: Role of ICAM-1 and ICAM-2 and alternate CD11/CD18 ligands in neutrophil transendothelial migration. J Leukoc Biol. 1999, 65 (1): 117-126.PubMedGoogle Scholar
- Van den Steen PE, Proost P, Wuyts A, Van Damme J, Opdenakker G: Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. Blood. 2000, 96 (8): 2673-2681.PubMedGoogle Scholar
- Vu TH, Werb Z: Gelatinase B: Structure, regulation, and function. Matrix Metalloproteinases. Edited by: Parks WC and Mecham RP. 1998, San Diego: Academic Press, 115-148.View ArticleGoogle Scholar
- Hickey M, Simbar M, Markham R, Young L, Manconi F, Russell P, Fraser IS: Changes in vascular basement membrane in the endometrium of Norplant users. Hum Reprod. 1999, 14 (3): 716-721. 10.1093/humrep/14.3.716.View ArticlePubMedGoogle Scholar
- Simbar M, Manconi F, Markham R, Hickey M, Fraser IS: A three-dimensional study of endometrial microvessels in women using the contraceptive subdermal levonorgestrel implant system, norplant. Micron. 2004, 35 (7): 589-595. 10.1016/j.micron.2004.01.005.View ArticlePubMedGoogle Scholar
- Hickey M, Carati C, Manconi F, Gannon BJ, Dwarte D, Fraser IS: The measurement of endometrial perfusion in norplant users: a pilot study. Hum Reprod. 2000, 15 (5): 1086-1091. 10.1093/humrep/15.5.1086.View ArticlePubMedGoogle Scholar
- Runic R, Schatz F, Wan L, Demopoulos R, Krikun G, Lockwood CJ: Effects of norplant on endometrial tissue factor expression and blood vessel structure. J Clin Endocrinol Metab. 2000, 85 (10): 3853-3859. 10.1210/jc.85.10.3853.PubMedGoogle Scholar
- Lockwood CJ, Kumar P, Krikun G, Kadner S, Dubon P, Critchley H, Schatz F: Effects of thrombin, hypoxia, and steroids on interleukin-8 expression in decidualized human endometrial stromal cells: implications for long-term progestin-only contraceptive-induced bleeding. J Clin Endocrinol Metab. 2004, 89 (3): 1467-1475. 10.1210/jc.2003-030141.View ArticlePubMedGoogle Scholar
Copyright
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.