Use of Human Fallopian Tube Organ in Culture (FTOC) and Primary Fallopian Tube Epithelial Cells (FTEC) to Study the Biology of Neisseria gonorrhoeae Infection.

Epithelial cells represent one of the most important physical barriers to many bacterial pathogens. In the case of Neisseria gonorrhoeae, the epithelial cell response is critical because they are the main target of the tissue damage triggered by the pathogen, particularly when the organism reaches the Fallopian tube (FT). Although the irreversible damage triggered by N. gonorrhoeae in the FT has been previously reported (ectopic pregnancy, pelvic inflammatory disease and infertility), the mechanisms of gonococcal-induced tissue damage are not fully understood. In addition, the lack of animal models that efficiently mimic the human disease and the complexity of gonococcus-host interactions make studying gonococcal pathogenesis particularly difficult. The use of human immortalized cells is also limited, since a variety of commercial FT cell lines is not yet available. Finally, the phase and antigenic variation of many gonococcal surface molecules involved in attachment and invasion of epithelial tissues leads to a failure to reproduce results using different human cells lines used in previous studies. The FT organ in culture (FTOC) and primary human fallopian tube epithelial cell (FTEC) represent the closest ex vivo cell models to explore the biology of Neisseria gonorrhoeae during infection of the FT, since it is a natural host target of the gonococcus. In this chapter, we describe protocols to process human FT samples to obtain FTOC and FTEC and assess their response to infection with Neisseria gonorrhoeae.

Increased expression of uteroglobin associated with tubal inflammation and ectopic pregnancy.

OBJECTIVE: Evaluation of uteroglobin (UG) expression in the fallopian tube in different tubal diseases. DESIGN: The UG was screened and quantified in samples of fallopian tubes from patients with salpingitis, hydrosalpinx, and ectopic pregnancy by exposing the UG with immunohistochemical techniques. SETTING: University hospital and electron microscopy center. PATIENT(S): Women with pelvic inflammatory disease (PID) and complicated tubal ectopic pregnancy consulting for medical care. INTERVENTION(S): Salpingectomy. MAIN OUTCOME MEASURE(S): Tubal tissues were collected and examined using regular pathologic techniques. The UG immunoreactivity in the tubal epithelium was also assessed. RESULT(S): Fallopian tube epithelium displayed an increased UG expression in patients with PID and complicated tubal pregnancy compared with control patients. CONCLUSION(S): Uteroglobin is present in the human fallopian tube as a secretory protein and appears to be involved in immunosuppressive responses in the fallopian tube.

Expression of MUC1 in tubal pregnancy.

The MUC1 mucin is normally expressed in the epithelium of the fallopian tube, and its expression on the epithelium of the tubes with ectopic pregnancies has not been studied. The mean (+/- SEM) histologic score for MUC1 was 1.4 +/- 0.2 in the luminal epithelium of tubes with ectopic pregnancies, and the histologic score for normal tubes was 2.8 +/- 0.2; however, these findings must be confirmed with the identification of the cytoplasmic tail of MUC1.

Expression of proinflammatory cytokines and receptors by human fallopian tubes in organ culture following challenge with Neisseria gonorrhoeae.

Infection of the Fallopian tubes (FT) by Neisseria gonorrhoeae can lead to acute salpingitis, an inflammatory condition, which is a major cause of infertility. Challenge of explants of human FT with gonococci induced mRNA expression and protein secretion for the proinflammatory cytokines interleukin (IL)-1alpha, IL-1beta, and tumor necrosis factor alpha (TNF-alpha) but not for granulocyte-macrophage colony-stimulating factor. In contrast, FT expression of IL-6 and of the cytokine receptors IL-6R, TNF receptor I (TNF-RI), and TNF-RII was constitutive and was not increased by gonococcal challenge. These studies suggest that several proinflammatory cytokines are likely to contribute to the cell and tissue damage observed in gonococcal salpingitis.

Inmunomodulación de factores producidos por las trompas de falopio de rata sobre la proliferación linfocitaria in vitro / Immunomodulation of factors produced by rat Fallopian tubes on the in vitro lymphocytic proliferation

Se plantea que la inducción de tolerancia inmune parece ser un mecanismo que participa en el normal funcionamiento del aparato genital femenino. Se propuso en este trabajo el estudio de la producción de sustancias inmunomoduladoras por las células epiteliales de las trompas de Falopio de rata en cultivo. Se obtuvieron las muestras de ratas y se cultivaron en medio RPMI 1 640 y en medio MEM D-val. Se colectó el medio y se le determinó la capacidad inmunomoduladora sobre la proliferación de linfocitos estimulados con mitógenos. Se comprobó que los cultivos realizados con RPMI 1 640 crecieron más rápido a predominio de células fusiformes, supuestamente fibroblastos, y brindaron una inhibición de la proliferación linfocitaria dosis dependiente y que aquellos cultivos donde se empleó el medio MEM D-val crecieron lentamente, con predominio de células redondeadas, presumiblemente epiteliales, y se inhibió la proliferación linfocitaria dosis dependiente lo cual permite inferir que las sustancias inmunomoduladoras son producidas fundamentalmente por las células epiteliales del lumen de las trompas, pudiendo ser este un mecanismo de tolerancia inmune que facilita el transporte de espermatozoides y del blastocito a través del oviducto(AU)

Is there a mucosal immune system associated with the mammalian oviduct?

The oviduct is a key component of the reproductive system where essential states such as spermatozoa capacitation, fertilization and early embryo development take place. Recently, an additional role for the entire female reproductive tract has emerged with important implications for our understanding and management of reproductive health, namely, its role in mounting local immune responses against microbial pathogens. Most of the evidence about mucosal immune responses in the female reproductive tract is related to the vagina, with less information available for the uterus. The less known segment in this regard is the oviduct, which prompted us to review and summarize the current state of knowledge on the immune system at the level of the mammalian oviduct. A comprehensive search was conducted in Medline and--for the last two years--also in Current Contents. Result demonstrate that the mammalian oviduct is endowed with many of the elements that characterize a mucosal immune system. However, there are gaps in our knowledge that, in addition to important interspecies differences, make it essential to explore further some fundamental questions regarding this system.

Is there a mucosal immune system associated with the mammalian oviduct?

The oviduct is a key component of the reproductive system where essential stages such as spermatozoa capacitation, fertilization and early embryo development take place. Recently, an additional role for the entire female reproductive tract has emerged with important implications for our understanding and management of reproductive health, namely, its role in mounting local immune responses against microbial pathogens. Most of the evidence about mucosal immune responses in the female reproductive tract is related to the vagina, with less information available for the uterus. The less known segment in this regard is the oviduct, which prompted us to review and summarize the current state of knowledge on the immune system at the level of the mammalian oviduct. A comprehensive search was conducted in Medline and -for the last two years- also in Current Contents. Results demonstrate that the mammalian oviduct is endowed with many of the elements that characterize a mucosal immune system. However, there are gaps in our knowledge that, in addition to important interspecies differences, make it essential to explore further some fundamental questions regarding this system.