Immunoregulatory activity, biochemistry, and phylogeny of ovine uterine serpin

PROBLEM: During pregnancy, the endometrium of the ewe secretes a progestero ne-induced member of the serpin superfamily of serine proteinase inhibitors called ovine uterine serpin (OvUS) that has immunosuppressive properties. METHOD: Review of the literature. RESULTS AND CONCLUSIONS: OvUS inhibits a wide variety of immune responses, including mixed lymphocyte reaction, mitogen-stimulated lymphocyte prolifer ation, and T cell-dependent antibody production. Recent data have suggested that OvUS functions by inhibiting protein kinase C and interleukin-2-media ted events. OvUS and similar genes present in cattle and pigs diverged from other serpins prior to the divergence of artiodactyls. Since this time, th e serpins have apparently undergone adaptive evolution that has led to a co nformational state and biological functions distinct from prototypical serp ins. Thus, it is likely that these proteins have an important role in the r eproductive biology of Artiodactyla. Several lines of evidence suggest that , in sheep, OvUS functions to mediate the immunosuppressive effects of prog esterone and prevent immunological rejection of the fetal allograft.