Female reproductive tract (FRT) epithelial cells protect against potential pathogens and sexually transmitted infections. The purpose of this study was to determine if epithelial cells from the upper FRT secrete antimicrobials that inhibit reproductive tract pathogens which threaten women's health. Apical secretions from primary cultures of Fallopian tube, uterine, cervical and ectocervical epithelial cells were incubated with Neisseria gonorrhoeae, Candida albicans (yeast and hyphal forms), HIV-1, and Lactobacillus crispatus, prior to being tested for their ability to grow and/or infect target cells. Epithelial cell secretions from the upper FRT inhibit N. gonorrhoeae and both forms of Candida, as well as reduce HIV-1 (R5) infection of target cells. In contrast, none had an inhibitory effect on L. crispatus. Cytokines and chemokines analysis in uterine secretions revealed several molecules that could account for pathogen inhibition. These findings provide definitive evidence for the critical role of epithelial cells in protecting the FRT from infections, without comprising the beneficial presence of L. crispatus, which is part of the normal vaginal microflora of humans.

Monoclonal and polyclonal, monospecific antibodies to the major surface antigen of Toxoplasma gondii (SAG-1, P30) inhibit infection of human fibroblasts and murine enterocytes. Fab prepared from polyclonal, monospecific antibody to P30 also have this inhibitory effect on invasion, which indicates that this antibody directly blocks parasite infection of host cells rather agglutinating the parasite. Antibodies to another surface protein (P22) did not alter in vitro infection. If the inhibitory effect of antibody to P30 was due to steric hindrance or complexing of surface epitopes contiguous to P30, antibodies to other surface epitopes would also be inhibitory and they are not. Urea treatment of antibody (which permits discrimination of high and low avidity antibody) did not alter the effect of anti-P30 antibody. This observation indicates that the effect of the antibody to P30 was not an artifact of differences in the avidity of the antibody to P22 and P30. Heat inactivated antisera from mice infected with either RH or PTg strain T. gondii (P30+) inhibit infection of fibroblasts when challenged with autologous wild-type parasites by 87 and 40%, respectively. In contrast, these antisera have little inhibitory effect (13 and 19%, respectively) against infection of human fibroblasts by a P30-deficient mutant (PTgB). Antisera raised to the P30-deficient mutant had no significant effect on infection of cells by wild-type strains that have surface P30. The neoglycoprotein, BSA-glucosamide, competitively blocks infection of human fibroblasts by P30+ tachyzoites with surface P30 in higher level than those without surface P30. This observation indicates that there is likely to be a glycosylated host cell receptor to which T. gondii's major surface Ag SAG-1 (P30) binds. Mice infected perorally develop intestinal IgA antibody to the major 30-kDa epitope of T. gondii. Thus, the major surface epitope of T. gondii, SAG-1 (P30), has an important, functional role in infection of host cells by T. gondii and elicits an intestinal antibody response after peroral infection.

In the present study the role of two families of cytochrome P-450 proteins and the contribution of the cytosolic fraction in the activation of N-nitrosopiperidine to mutagens in the Ames test were investigated. The bioactivation of this nitrosamine was preferentially catalysed by the phenobarbitone-induced cytochromes P-450, in contrast to the 3-methylcholanthrene-induced cytochromes P-448. The mutagenicity of nitrosopiperidine catalysed by microsomes, in the absence of cytosol, was lower when compared with that observed with S9 fractions. Cytosol itself could not activate nitrosopiperidine but potentiated the microsome-mediated mutagenicity of the carcinogen. The cytosolic potentiation was still evident when microsomal metabolism was terminated, indicating that cytosolic enzyme(s) can further convert the microsome-generated metabolites to more potent mutagens. The cytosolic enzyme(s) was inducible by prior treatment of the rats with phenobarbitone or Arochlor 1254 but not 3-methylcholanthrene. The microsome-mediated activation of nitrosopiperidine could be supported by NADH in the absence of NADPH. It is therefore concluded that the activation of nitrosopiperidine to mutagen(s) involves, in addition to NADH- and NADPH-dependent microsomal enzymes, cytosolic proteins.

Hepatic microsomal mixed-function oxidase activities and the metabolic activation of chemical carcinogens to mutagens in the Ames test were investigated using Aroclor 1254-induced rat and hamster preparations. Benzphetamine N-demethylase, NADPH-cytochrome c reductase and cytochromes P-450 and b5 were induced in both animals to the same extent by pre-treatment with Aroclor. However, the O-deethylation of ethoxyresorufin was markedly induced in the rat (147-fold) but only modestly in the hamster (3-fold). 1,2-Benzanthracene and 4-aminobiphenyl were more efficiently activated by the rat preparations while, in contrast, 2-acetylaminofluorene, 2-aminoanthracene, nitrosopiperidine, nitrosopyrrolidine, cyclophosphamide and phenacetin were more efficiently activated by the hamster preparations. No significant difference was observed in the activation of 3-methylcholanthrene, benzo[a]pyrene and 2-aminofluorene. It is concluded that (a) the hamster is relatively refractive to cytochrome P-448 induction, and (b) Aroclor 1254-induced rat and hamster S9 preparations differ in their ability to convert chemical carcinogens to mutagens in the Ames test.

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