title: Interferon beta-1a prevents the effects of lipopolysaccharide on embryonic brain microvessels.
abstract: By means of light and electron microscopy we have studied the effect of interferon beta-1a (IFNbeta-1a) in the optic tecta of 20-day-old chick embryos under normal conditions and after exposure to lipopolysaccharide (LPS) which mimics the blood-brain barrier (BBB) disruption in meningoencephalitis. Optic tecta were examined for: (i) ultrastructure by means of transmission electron microscopy; (ii) the immunohistochemical localization of HT7 antigen, a specific marker of differentiation of the brain microvessels; (iii) the brain microvessel permeability, by means of horseradish peroxidase (HRP) tracer; (iv) the expression of microvessel glycoconjugates, by means of lectin histochemistry, using Ricinus communis agglutinin-I (RCA-I), specific for beta-D-galactosyl moieties and Wheat Germ agglutinin (WGA) specific for sialyl and N-acetylglucosaminyl moieties. A morphometric evaluation of brain microvessel permeability and of glycoconjugate expression was also performed. In control- and in IFNbeta-1a-treated embryos, HRP was confined to the vessel lumina which were sealed by the interendothelial tight junctions. RCA-I binding sites were recognizable both in the basal membranes and in the tight junctions, while WGA sites were present on the luminal side of the endothelial cells. HRP was blocked in the vessels lumina by the interendothelial tight junctions. After LPS treatment, HRP showed an extravascular localization and the labeling of microvessels by anti-HT7 antibodies disappeared. RCA-I binding was only found ultrastructurally and appeared as irregularly clustered gold particles, in the cleft of damaged tight junctions, but were no longer detectable in the endothelial basement membranes. After pretreatment of LPS-treated embryos with IFNbeta-1a, the vessel permeability to HRP strongly decreased and the vessels showed the normal pattern of HT7 protein and of the RCA-I binding sites. These results indicate that the changes induced by LPS in the endothelial cells are prevented by IFNbeta-1a.
authors.affiliation: Institute of Human Anatomy, Histology and Embryology, University of Bari Medical School, Policlinico, Piazza G. Cesare, 11, I-70124, Bari, Italy. nico@histology.uniba.it
authors.forename: B
authors.initials: B
authors.lastname: Nico
authors.forename: F
authors.initials: F
authors.lastname: Quondamatteo
authors.forename: R
authors.initials: R
authors.lastname: Herken
authors.forename: T
authors.initials: T
authors.lastname: Blumchen
authors.forename: G
authors.initials: G
authors.lastname: Defazio
authors.forename: M
authors.initials: M
authors.lastname: Giorelli
authors.forename: P
authors.initials: P
authors.lastname: Livrea
authors.forename: A
authors.initials: A
authors.lastname: Marzullo
authors.forename: G
authors.initials: G
authors.lastname: Russo
authors.forename: D
authors.initials: D
authors.lastname: Ribatti
authors.forename: L
authors.initials: L
authors.lastname: Roncali
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000970:Antineoplastic Agents / Q000494:pharmacology*; D030161:Avian Proteins; D051926:Basigin; D015415:Biomarkers; D001798:Blood Proteins; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000196:embryology*; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins / Q000032:analysis; D008833:Microcirculation / Q000187:drug effects; D008854:Microscopy, Electron
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D030161:Avian Proteins; D015415:Biomarkers; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D051926:Basigin; D016899:Interferon-beta; D006735:Horseradish Peroxidase; D000068556:Interferon beta-1a