COMPARISON OF INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION IN THE BRAINS OF LISTERIA MONOCYTOGENES-INFECTED CATTLE, SHEEP, AND GOATS AND IN MACROPHAGES STIMULATED IN-VITRO

The expression of inducible nitric oxide synthase (iNOS) was studied i n the brains of cattle, sheep, and goat that succumbed to a natural in fection with Listeria monocytogenes. The lesions in infected brains ar e characterized by microabscesses, perivascular cuffs, gliosis, glial nodules, and large areas of malacia. Using immunocytochemistry, we det ected bacteria in microabscesses, particularly in sheep and goats, and in areas without signs of inflammation, but not in perivascular infil trates. iNOS was expressed by macrophage (M phi)-type cells of microab scesses and glial nodules but rarely by M phi in areas of malacia, as determined by immunohistochemistry with iNOS-specific antibodies. iNOS was not detected in perivascular cuffs. Major histocompatibility comp lex class II molecules (MHC-II), another marker of cell activation, sh owed a different pattern of distribution, Perivascular cuffs contained high numbers of MHC-II-positive cells, including some with M phi char acteristics, Microabscesses in sheep and goats showed low expression o f MHC-II, particularly in iNOS-expressing cells, In cattle, the expres sion of markers for activated or recruited phagocytes, the calcium-bin ding proteins S100A8 and S100A9 (formerly called MRP-8 and MRP-14, res pectively), was largely restricted to cells showing weak or undetectab le iNOS expression; iNOS-positive M phi showed a low expression of S10 0A8 and S100A9. Thus, iNOS is expressed by a restricted subset of M ph i in listeric encephalitis. In cultured sheep and goat M phi, a low pr oportion of cells expressed iNOS upon activation by L. monocytogenes a nd gamma interferon, resulting in nitrite generation at least 1 order of magnitude lower than that in similarly treated cattle M phi. Since these species differences were much less obvious in vivo, it appears t hat the well-known species variation in iNOS expression by M phi could reflect an in vitro phenomenon.