Uterine Mast Cell Research Articles

Lack of Annexin A1 Exacerbates Inflammatory Response in Acute Endometritis Model.

Annexin A1 (AnxA1) is a glucocorticoid-inducible protein and an important endogenous modulator of inflammation. However, its effect in the endometrial microenvironment is poorly explained. This study aimed to evaluate the role of endogenous AnxA1 in an endometritis mouse model induced by lipopolysaccharide (LPS). Female C57BL/6 wild-type (WT) and AnxA1-/- mice were divided into two groups: SHAM and LPS. To induce endometritis, mice received a vaginal infusion of 50 μL of LPS (1 mg/mL) dissolved in phosphate-buffered saline. After 24 h, the mice were euthanized, and blood and uteri samples were collected. The endometrium inflammatory scores were significantly increased in the LPS-treated group. AnxA1-/- mice from the LPS group demonstrated a significant increase in the number of degranulated mast cell levels compared to AnxA1-/- SHAM mice. The Western blotting analysis revealed that a lack of AnxA1 promoted the upregulation of NLRP3 and pro-IL-1β in the acute endometritis animal model compared to WT LPS animals. LPS-induced endometritis increased the number of blood peripheral leukocytes in both WT and AnxA1-/- mice compared with SHAM group mice (p < 0.001). AnxA1-/- mice also showed increased plasma levels of IL-1β (p < 0.01), IL-6, IL-10, IL-17, and TNF-α (p < 0.05) following LPS-induced endometritis. In conclusion, a lack of endogenous AnxA1 exacerbated the inflammatory response in an endometritis model via NLRP3 dysregulation, increased uterine mast cell activation, and plasma pro-inflammatory cytokine release.

Retraction note: Uterine mast cell tumor: a clinical and cytohistopathological study.

Mast cells are one of the characteristic factors in angiogenesis, growth, and metastatic spread of tumors. Further studies are suggested to determine the type of these cells which might be useful in the assessment of biological nature of the tumor and its future treatment modality. Few studies have evaluated mast cell infiltration in visceral tumors, especially uterine tumors. In this study, age, sex, death rate, and histologic patterns were in agreement with those of previous reports on canine mast cell tumors. Cytopathology assays are widely used to prognosticate canine uterine mast cell tumors (MCT). There is limited information about these prognostic assays used on MCT that arise in the uterine. The anisocytosis and anisocytosis and giant cells were present in the tumor. Furthermore, the tumor had nuclear atypia with scattered multinucleated cells and prominent nucleoli and tumor were classified as poorly granulated. Under microscopic examination, we observed diffuse infiltration and proliferation of tumor cells from the uterine different area and the infiltrative characteristics and distribution patterns of neoplastic cells were observed. This tumor consisted of sheets and cords of uniform round cells with discrete cytoplasmic margins. Microscopically, the neoplastic masses were poorly-demarcated and lacked capsules and tumor cell usually showed a distinct cell boundary. Nevertheless, the neoplastic cells were located between collagen bundles forming small clusters and sheets and had large, centrally located, round to ovoid nuclei. In addition, eosinophils were scattered among the mast cells at the periphery of the masses. The presence of eosinophils and the observation, at high magnification, of cells with cytoplasmic metachromatic granules. Based on these findings, a diagnosis of poorly-differentiated mast cell tumor was made and data histologic grading was available for tumor. Neoplasm was poorly differentiated or gradeIII.

Uterine mast cell tumor: a clinical and cytohistopathological study

BackgroundMast cells are one of the characteristic factors in angiogenesis, growth, and metastatic spread of tumors. Further studies are suggested to determine the type of these cells which might be useful in the assessment of biological nature of the tumor and its future treatment modality. Few studies have evaluated mast cell infiltration in visceral tumors, especially uterine tumors.Case presentationIn this study, age, sex, death rate, and histologic patterns were in agreement with those of previous reports on canine mast cell tumors. Cytopathology assays are widely used to prognosticate canine uterine mast cell tumors (MCT). There is limited information about these prognostic assays used on MCT that arise in the uterine. The anisocytosis and anisocytosis and giant cells were present in the tumor. Furthermore, the tumor had nuclear atypia with scattered multinucleated cells and prominent nucleoli and tumor were classified as poorly granulated. Under microscopic examination, we observed diffuse infiltration and proliferation of tumor cells from the uterine different area and the infiltrative characteristics and distribution patterns of neoplastic cells were observed. This tumor consisted of sheets and cords of uniform round cells with discrete cytoplasmic margins. Microscopically, the neoplastic masses were poorly-demarcated and lacked capsules and tumor cell usually showed a distinct cell boundary. Nevertheless, the neoplastic cells were located between collagen bundles forming small clusters and sheets and had large, centrally located, round to ovoid nuclei. In addition, eosinophils were scattered among the mast cells at the periphery of the masses. The presence of eosinophils and the observation, at high magnification, of cells with cytoplasmic metachromatic granules.ConclusionBased on these findings, a diagnosis of poorly-differentiated mast cell tumor was made and data histologic grading was available for tumor. Neoplasm was poorly differentiated or gradeIII.

Successful treatment of mast cell sarcoma of the uterus with imatinib

Mast cell sarcoma is a rare disease characterized by localized, but destructive and rapid, growth of the tumor, high risk of distant metastasis, possibility of a leukemic phase, and poor prognosis. We report successful treatment of uterine mast cell sarcoma with imatinib in a 39-year-old woman who presented with abdominal distention and massive ascites. Routine treatment, such as combined chemotherapy, had little effect. We administered imatinib to the patient and achieved a good response in the absence of c-kit mutation, BCR/ABL, and FIP1L1-PDGFRα. Our results indicate that imatinib is of potential use in the treatment of mast cell sarcoma.

Uterine autonomic nerve innervation plays a crucial role in regulating rat uterine mast cell functions during embryo implantation

To explore the potential mechanism of how uterine innervations would affect the uterine mast cell (MC) population and functions during the periimplantation. We herein first examined the consequence of uterine neurectomy on embryo implantation events. We observed that amputation of autonomic nerves innervating the uterus led to on-time implantation failure in rats. Exploiting MC culture and ELISA approaches, we then further analyzed the effect of neurectomy on cellular histamine levels and its release from uterine MCs, to elucidate the relation of the autonomic nerves and local cellular immunity in the uterine during early pregnancy. We observed that disconnection of autonomic nerve innervation significantly increased the population of uterine MCs. Most interestingly, these increased number of uterine MCs in neuroectomized rats contained a much reduced cellular level of histamine. Our subsequent challenge experiments revealed that uterine MCs in nerve amputated rats exhibited enhanced histamine releasing rate in response to substance P and antiIgE, suggesting loss of nerve innervation in the uterus not only increases the population of uterine MCs, but also facilitates the release of histamine from MCs, thus subsequently interfere with the normal implantation process. Collectively, our findings provide a new line of evidence supporting the concept that immune–neuro-endocrine network plays important role during pregnancy establishment and maintenance.

Degranulation of uterine mast cell modifies contractility of isolated myometrium from pregnant women

This study was undertaken to test that uterine mast cell degranulation alters human myometrial contractility in vitro and to define what mediators are involved in this process. Longitudinal myometrial strips prepared from biopsy specimen obtained from the lower uterine segment of women at preterm and term gestation (with and without labor) were studied. Contractile responses to compound 48/80, a mast cell degranulator, were compared in the absence or presence of a mast cell stabilizer, H 1 and H 2 receptor antagonists, cyclooxygenase, and lipoxygenase inhibitors. Compound 48/80 increased myometrial contractility in all groups. The mast cell stabilizer cromolyn inhibited contractility, whereas the cyclooxygenase inhibitor ibuprofen, the H 1 -receptor antagonist S(+)-chlorpheniramine maleate, but not the H 2 antagonist cimetidine, only slightly attenuated this effect. The lipoxygenase inhibitor linoleyl hydroxamic acid augmented the responses to compound 48/80 in the preterm but not in the term group. Uterine mast cell degranulation, or the effects of their mediators, can modulate uterine contractility during pregnancy.

Stress triggered abortions are associated with alterations of granulated cells into the decidua.

Stress is known to be abortogenic in animals and humans. An increased decidual release of cytokines such as TNF-alpha and reduction in TGF-beta 2-related immunosuppressive activity has been proposed as the triggering mechanism. Substance P release by nerves in endometrium/decidua has been found to be the key neurotransmitter in this pathway. It is still unclear which cells are stimulated by substance P to produce the increased TNF-alpha level. As a measure of local activation, the granulation of granulated material gland (GMG) cells was measured by flow cytometry after sonic plus immobilization stress of mice or substance P treatment of GMG cells (both isolated GMG cells and GMG-cell containing decidua). TNF-alpha release from decidua and isolated GMG cells was investigated using a TNF-alpha bioassay. The degranulation of uterine mast cell, another potential source of TNF-alpha, was examined in situ by Toluidine blue staining. We observed a striking increase in percentage of degranulated mast cells (8% -->24%) in the uteri of stressed animals, whereas the granularity of GMG cells was decreased by stress but increased with treatment with substance P in vitro. Isolated GMG cells appeared to release in vitro cytotoxins active in the TNF-alpha bioassay, but the magnitude of this activity was not increase by stress or by substance P treatment. In contrast, disaggregated decidual tissue which is known to release increased amounts of TNF-alpha after stress, did increase activity in response to substance P in vitro. Uterine mast cells show activation as reflected by degranulation after stress exposure of pregnant mice and mast cells might be the cellular link between the neurotransmitter substance P and increase in decidual TNF-alpha release that leads to abortion.

A factor secreted by human embryo stimulates cytokine release by uterine mast cell.

The existence of a biochemical network of embryo-maternal communication implies that various secreted molecules constitute a signal-response mechanism, important for the process of embryo implantation in mammals. Here we report the purification of a protein with an apparent molecular weight of 136 kDa, responsible for a 2000-fold increase in embryo-derived histamine-releasing factor (EHRF) activity. This protein, purified from medium from the in-vitro culture of 2-8-cell human embryos, by means of affinity chromatography, was capable of binding immunoglobulin (Ig)E as demonstrated by immunoblotting and enzyme-linked immunosorbent assays. We found EHRF was capable of inducing release of histamine and cytokines in vitro from rat uterine tissue, collected on day 4 of pregnancy (preimplantation stage of embryo development). When EHRF was used as a secretagogue, granulocyte macrophage-colony stimulating factor (GM-CSF) release increased from 3 to 55 pg/g (P < 0.01) and tumour necrosis factor-alpha (TNF-alpha) release increased from 0 to 2.1 ng/g (P < 0.01), as detected by enzyme-linked immunosorbent assay. A simple method was used to purify uterine mast cells using an IgE-Sepharose affinity chromatography column and the purity (90%) was checked with Dynabeads coupled to specific rat IgE antibody. When purified mast cells were stimulated with EHRF in the same way as the uterine explants, a similar pattern of GM-CSF and TNF-alpha release was obtained. We also describe the reverse transcription-polymerase chain reaction (RT-PCR) of GM-CSF and TNF-alpha mRNA from purified uterine mast cells. On day 4 of pregnancy only the mRNA of TNF-alpha was found and this increased after stimulation with the EHRF. In conclusion, the data presented suggest that uterine mast cells isolated during the preimplantation stage release cytokines in vitro following interaction with an embryo factor.

Effect of Substance P on uterine mast cell cytokine release during the reproductive cycle

There is increasing evidence that neuropeptides, steroid hormones and inflammatory cytokines influence the immune response during the reproductive cycle. In the present study, we focus on the effects of neuropeptide Substance P (SP) during the pre-implantation stage of embryo development (day 4 of pregnancy), at pro-estrus and di-estrus (two phases with different hormonal states). We found heterogeneous responses to SP and anti-IgE by the rat uterine mast cells (MCs), as detected by ELISA. In fact, MCs purified from uteri on day 4 of pregnancy released histamine, granulocyte macrophage-colony stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-α) in response to anti-IgE, but not to SP. When pre-incubated with SP, the release to anti-IgE was significantly enhanced compared to anti-IgE alone. Exposure of SP to antibodies to SP, prior to pre-incubation with MCs, negated the SP effect on IgE-mediated release. At the pro-estrus phase SP showed similar behavior as on day 4 of pregnancy, whereas at the di-estrus phase SP alone was capable of inducing release of histamine and cytokines from purified uterine MCs. Moreover, non-quantitative RT-PCR analysis of the TNF-α mRNA level suggested an SP stimulation at the di-estrus phase, but neither on day 4 of pregnancy nor at the pro-estrus phase. Taken together, these data strongly suggest that SP can modulate IgE-mediated uterine MC release of histamine and inflammatory cytokines in different ways, depending on the phase of the reproductive cycle.

Postcoital Contraceptive Effects of an Alcoholic Extract of the Daucus carota Linn Seed in Rats

The alcoholic extract of Daucus carota Linn (carrot) seed was administered at different doses ranging from 50 to 250 mg/kg. Bodyweight after coitus showed a significant antifertility effect, which was dose dependent. The administration of this extract at a lower dose showed anti-implantational activity, whereas higher doses caused fetus resorption. The main effect of the extract appears to be an abortifacient activity. At higher dose levels the extract demonstrated an estrogenic nature with a prolonged estrous phase, whereas lower doses showed an antiestrogenic nature and an increase in the percentage duration of the diestrous phase of the estrous cycle. This extract is neither progestational nor antiprogestational. A uterine mast cell study directly reflected the hormonal nature of the extract and the mode of antifertility activity in rats.

Role of uterine mast cell in neuroimmunoendocrine events at embryo implantation

Role of uterine mast cell in neuroimmunoendocrine events at embryo implantation

Role of uterine mast cell in neuroimmunoendocrine events at embryo implantation

Role of uterine mast cell in neuroimmunoendocrine events at embryo implantation

Human uterine mast cells. Isolation, purification, characterization, ultrastructure, and pharmacology.

As part of an ongoing investigation of human mast cell heterogeneity, we have isolated, partially purified, and characterized the uterine mast cell and compared it with mast cells isolated from other organs. The average histamine content of myometrium and leiomyofibroma obtained from hysterectomies was 2.1 +/- 0.3 (mean +/- SEM) microgram/g of tissue (n = 10), and the histamine content of the two tissues did not differ significantly. A mild collagenase, hyaluronidase, and DNase digestion was used to disperse the uterine mast cells, with an average yield of 9.5% (range, 0 to 21%). The average histamine/uterine mast cell was 2.1 +/- 0.2 pg (n = 3), and 61 +/- 7% (n= 3) of the uterine mast cells survived overnight culture. Early purification efforts with Percoll gradients have yielded up to 80% pure uterine mast cells, with an average of 27 +/- 10% (n = 5). Uterine mast cells released histamine in response to the secretogogues anti-IgE and A23187 but did not respond to substance P or to the basophil secretogogues FMLP, C5a, and 12-O-tetradecanoylphorbol-13-acetate. After 1 microgram/ml anti-IgE stimulation, the uterine mast cell appeared to make significant quantities of PGD2 (89 +/- 26 ng/10(6) cells, n = 6) (p less than 0.05), as assayed by RIA. Simultaneously, leukotriene C4 release was 45 +/- 15 ng/10(6) cells, (n = 6) (p less than 0.05), as assayed by RIA. Combined gas-chromatography mass spectroscopy analysis of anti-IgE-stimulated cell supernatants confirmed the production of PGD2. In pharmacologic studies, isobutyl-methylxanthine and isoproterenol blocked anti-IgE-induced histamine release. The uterine mast cell is similar to the lung mast cell in terms of response to secretogogues and release of arachidonic acid metabolites. Ultrastructurally, the uterine mast cell contains scroll granules, crystal granules, combined granules, homogeneously dense granules, and large lipid bodies, many with focal lucencies within them. Particle granules, most frequently present in gut mast cells of mucosal origin, were absent from uterine mast cells. Although certain features are analogous to the ultrastructure of skin or lung mast cells, the combination of structures is distinctive for uterine mast cells.

The human skin mast cell: A comparison with the human lung cell and a novel mast cell type, the uterine mast cell

The functional and histochemical properties of isolated mast cells from human skin, uterine myometrium and lung parenchyma were compared. The skin cell showed a marked difference in responsiveness to both secretagogues and anti-allergic compounds when compared to mast cells from the uterus and lung. The latter cell types responded more strongly to immunologically-directed ligands and calcium ionophores than the skin cell. However, the skin cell released histamine in response to a wide variety of polycationic compounds whilst the lung and uterine cells were essentially refractory to these agents. The antiallergic drugs, disodium cromoglycate (DSCG) and nedocromil sodium, were weakly inhibitory against the skin cell but were in contrast more effective against the lung and uterine cells.

The effect of an intrauterine device on mast cell numbers and distribution in the hamster uterus.

The effect of an IUD on mast cell numbers and distribution in the uterus was studied in castrated, castrated hormone-treated and cycling hamsters. The device had a stimulatory effect on total mast cell numbers in those animals that received no treatment, peanut oil, or estrogen therapy and in all cycling animals. The device also apparently causes mast cells to be redistributed in the different areas of the uterus. The results indicate that the IUD alters the uterine mast cell response to exogenous hormones and cycle times.

The effects of pregnancy and wounding on the mast cell population of the rat uterus.

SummaryThe uterine mast cell population has been observed in virgin, parous, and pregnant rats.The mast cell population of the uterus was also studied after vaginal delivery and hysterotomy.An increase in the number of mast cells was observed during pregnancy but this was not statistically significant.A significant increase in mast cell numbers occurred in the puerperium whether delivery was per vaginam or by hysterotomy.

MAST CELL DISTRIBUTION IN THE UTERUS OF CYCLING AND PREGNANT HAMSTERS.

AbstractIn this study the distribution of mast cells in the cephalic, middle, or caudal portions of the uterine horns did not differ. In cross‐sections, however, mast cells were most numerous in the myometrium, intermediate in the tunica vasculare of the endometrium and least in the mucosa. In the endometrium, the mast cells were most numerous in the antimesometrial, least in the mesometrial and intermediate in the lateral quadrants. In the myometrium, however, the relative numbers of mast cells between the quadrants varied according to the day in the estrous cycle.On days 1 (the day after estrus), 2, 3, and 4, (the day of proestrus) of the estrous cycle, there were respectively 42.7, 21.8, 22.5 and 10.7 mast cells in the endometrium per 12 μ sections. The differences in means between groups was highly significant (P &lt; 0.001). In mated females on 67, 79, 91, 103, 115, and 151 hours after ovulation, there were respectively 9.4, 8.4, 4.7, 5.6, 2.1, and 2.2 mast cells in the endometrium per 12 μ cross‐section. The differences in the means were not significant.The mean number of mast cells per 12 μ cross‐sections of uteri of ovariectomized females was 20 ± 8. Subcutaneous injections of 0.3 gamma estrogen did not significantly alter the number of mast cells but 0.6 gamma depressed the mean count to 11 ± 7.It appeared from these studies that the uterine mast cell numbers were related to the cyclic phenomena of estrous, but that the numerical relationship to the time of nidation was not clear.

Inhibition of decidual cell formation in the pseudopregnant rat by histamine antagonists.

ArticleInhibition of Decidual Cell Formation in the Pseudopregnant Rat by Histamine AntagonistsM. C. ShelesnyakM. C. ShelesnyakFrom the Department of Experimental Biology, Weizmann Institute of Science Rehovoth, IsraelPublished Online:01 Sep 1952https://doi.org/10.1152/ajplegacy.1952.170.3.522MoreSectionsPDF (826 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByNerve-sparing abdominal radical trachelectomy: a novel concept to preserve uterine branches of pelvic nervesEuropean Journal of Obstetrics & Gynecology and Reproductive Biology, Vol. 193Reflections on Rodent ImplantationPossible Effect of Histamine in Physiology of Female Reproductive Function: An Updated Review20 September 2010Uterine autonomic nerve innervation plays a crucial role in regulating rat uterine mast cell functions during embryo implantationProstaglandins & Other Lipid Mediators, Vol. 90, No. 3-4Monoamine transporters in human endometrium and decidua5 November 2008 | Human Reproduction Update, Vol. 15, No. 2Effect of Substance P on uterine mast cell cytokine release during the reproductive cycleJournal of Neuroimmunology, Vol. 60, No. 1-2Implantation and decidualization in rodentsJournal of Experimental Zoology, Vol. 266, No. 6D4H-ImplantationIdentification of a histamine-releasing factor secreted by human pre-implantation embryos grown in vitroJournal of Reproductive Immunology, Vol. 13, No. 1A History of Research on NidationAnnals of the New York Academy of Sciences, Vol. 476, No. 1 NidationThe effects of histamine dihydrochloride on blastocyst implantation in the laboratory ratExperientia, Vol. 36, No. 10The Role of Progesterone in Induction of Decidualization in the Uterus of the Pseudopregnant RatHistamine receptors on rabbit blastocyst and endometrial cell membranes1 April 1979 | Nature, Vol. 278, No. 5705The Effect of Prostaglandins F2α And E2 on Pregnancy in Mice During ImplantationFertility and Sterility, Vol. 30, No. 3Decidual extracts suppress antibody response in vitroEuropean Journal of Immunology, Vol. 7, No. 2HistaminkreisSchlußbetrachtungen und AusblickeBesonderheiten der Wirkungen der einzelnen Gestagene auf Morphologie und Funktion des GenitaltraktesStudies on the mechanism of nidation XXX: selective antihistaminic inhibition of uterine responses in relation to suppression of decidualizationLife Sciences, Vol. 6, No. 11Benzhydrylpiperazine antihistamines, hydramnios, and congenital malformations in the ratAmerican Journal of Obstetrics and Gynecology, Vol. 93, No. 4Histamine in Human Development12 November 2008 | Developmental Medicine & Child Neurology, Vol. 7, No. 3A TUMOUR TISSUE ANALOGUE OF THE IMPLANTING MOUSE EMBRYO*30 October 2009 | Proceedings of the Zoological Society of London, Vol. 141, No. 1Antihistamine drugs on rat pregnancy: Effects of pyrilamine and meclizineLife Sciences, Vol. 2, No. 5Failure of Histamine to induce Deciduomata in the RatNature, Vol. 194, No. 4828The incidence of experimentally produced abdominal implantations in the ratThe Anatomical Record, Vol. 141, No. 2The failure of antihistamines to suppress nuclear polyploidy in regenerating mouse liverThe Journal of Pathology and Bacteriology, Vol. 80, No. 1Prevention of pregnancy by the graefenberg ring methodAmerican Journal of Obstetrics and Gynecology, Vol. 78, No. 2COMPARATIVE POTENCY OF SEVERAL PROGESTOGENIC COMPOUNDS IN A BATTERY OF DIFFERENT BIOLOGICAL TESTSAnnals of the New York Academy of Sciences, Vol. 71, No. 5 New Steriod C More from this issue > Volume 170Issue 3September 1952Pages 522-527 Copyright & PermissionsCopyright © 1952 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1952.170.3.522PubMed12985926History Received 27 May 1952 Published online 1 September 1952 Published in print 1 September 1952 Metrics