|Seals, Richard - B.A.S.|
|Wulster-Radcliffe, Meghan - B.A.S.|
Submitted to: Journal of Reproductive Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 4, 2002
Publication Date: May 7, 2003
Citation: Seals, R.C., Wulster-Radcliffe, M.C., Lewis, G.S. Uterine response to infectious bacteria in estrous cyclic ewes. American Journal of Reproductive Immunology. 2003. v.49. p. 269-278. Interpretive Summary: Nonspecific uterine infections are a serious problem in livestock all over the world. Based on this and our other studies, the ability of the uterus to resist an infection (i.e., activation of the uterine immune system) is highly dependent upon changes in steroid concentrations, particularly progesterone, because only luteal-phase ewes inoculated with bacteria developed infections in this study. Also, a proper PGE2:PGF2a ratio (both compounds are arachidonic acid metabolites) may be important in uterine immune cell function. Bacterial inoculation and in vitro treatment with PGE2 suppressed, whereas PGF2a enhanced, Con A-stimulated lymphocyte proliferation. This seems to signify the involvement of bacterial products and prostaglandins in uterine immune regulation. Thus, manipulating arachidonic acid metabolites may provide us with a prevention or treatment plan for uterine infections that are superior to those currently available, which typically rely on antibiotics and antimicrobials.
Technical Abstract: Luteal-phase uteri are susceptible to infections, and PGE2 and exogenous progesterone can down-regulate, whereas PGF2a can up-regulate, uterine immune functions. To study this phenomenon, uteri of follicular- or luteal-phase ewes were inoculated with either saline or bacteria (Arcanobacterium pyogenes and Escherichia coli). Vena caval progesterone, PGE2, and PGF2a were measured. Lymphocytes from vena caval blood samples were assigned to a 2 x 2 factorial array of treatments (10[E-7] M PGE2 [Exp. 1], 10[E-7] M PGF2a [Exp. 2], and 10[E-7] M indomethacin [INDO] were main effects), and proliferation was quantified. In Exp. 1, progesterone was greater (P < 0.01) in luteal than in follicular ewes (3.4 vs 0.4 ng/mL), and only follicular ewes inoculated with bacteria developed infections. Lymphocyte proliferation was least (P = 0.08) in follicular ewes (2.6 vs 4.5 pmol for follicular and luteal, respectively). Concanavalin A (Con A)-stimulated proliferation was less (P < 0.05) for ewes inoculated with bacteria and for cells cultured with diluent (5.9 vs 3.1 pmol for saline and bacteria, respectively) or with INDO (6.6 vs 2.8 pmol for saline and bacteria, respectively). Also, Con A-stimulated lymphocytes from ewes inoculated with bacteria tended to proliferate less (P < 0.1) when cultured with PGE2 (4.9 vs 3.7 pmol for saline and bacteria, respectively) or PGE2 + INDO (5.5 vs 3.8 pmol for saline and bacteria). In Exp. 2, progesterone was greater (P < 0.01) in luteal than in follicular ewes (6.5 vs 1.2 ng/mL), and only follicular ewes inoculated with bacteria developed infections. Concanavalin A-stimulated lymphocyte proliferation was greater (P < 0.001) for follicular ewes (3.1 vs 4.1 pmol for luteal and follicular, respectively). Lymphocytes collected from follicular ewes proliferated more (P < 0.01) when cultured with PGF2a (2.7 vs 3.5 pmol for follicular and luteal, respectively), but INDO did not affect unstimulated or mitogen-stimulated proliferation. In conclusion, PGE2 suppressed, whereas PGF2a enhanced, lymphocyte proliferation. Bacterial inoculation and in vitro treatment with PGE2 suppressed lymphocyte proliferation and may signify the involvement of bacterial products and prostaglandins in uterine immunity regulation.