COMPARATIVE LOCALIZATION OF ENDOTHELIAL AND INDUCIBLE NITRIC-OXIDE SYNTHASE ISOFORMS IN HAEMOCHORIAL AND EPITHELIOCHORIAL PLACENTAE

The presence and immunolocalization of type II (inducible or macrophag e) and type III (endothelial) nitric oxide synthase (NOS) isoforms wer e compared in the term placentae of humans, rhesus monkeys, baboons, g uinea-pigs, rats and sheep using isoform specific antibodies. In the h uman placenta, intense immunohistochemical staining for type III NOS w as seen in syncytiotrophoblast with weaker staining in vascular endoth elial cells. Only vascular endothelial cells showed positive type III NOS staining in rhesus monkey, baboon, guinea-pig, rat and sheep place ntae. No positive type III NOS immunostaining was seen in trophoblast from any non-human placentae. Western blotting revealed a 135-kDa type III NOS species in placental homogenates, semi-purified by ADP-sephar ose affinity chromatography, from all the species tested confirming an tibody specificity. Type II NOS immunostaining-was localized to certai n villous stromal cells which also stained for CD14 (a monocyte/macrop hage marker) in the placenta of humans, rhesus monkeys, baboons and sh eep. No specific immunohistochemical staining for type II NOS or CD14 was noted in the two rodent species, guinea-pig and rat. On Western bl ots, a 130-kDa type II NOS species was identified in semi-purified pla cental homogenates of every species except guinea-pig, although weak b ands were seen for rhesus monkey and baboon. The failure of the antibo dies to show type II NOS in the rat placenta by immunohistochemistry m ay be due to a difference in antigen conformation from Western blots. As only human placental syncytiotrophoblast expresses type III NOS, th e putative functions ascribed to this isoform in syncytiotrophoblast, i.e. to prevent platelet and leucocyte aggregation in the intervillous space and adhesion to the trophoblast surface or to mediate peptide h ormone release from trophoblast, may be unique to humans. Alternativel y, syncytiotrophoblast-derived NO may fulfil some other unknown functi on. The similar pattern of expression of type II NOS in those species with villous fetomaternal interdigitation and multivillous fetomaterna l blood flow interrelations may represent a more universal role in sur veillance and/or protection against maternal insults or pathogens by i mmunologic activation and subsequent synthesis of nitric oxide which e xerts a cytostatic/cytotoxic response. (C) 1997 W. B. Saunders Company Ltd.