title: Altered signal pathway in angiotensin II-stimulated neutrophils of patients with hypercholesterolaemia.
abstract: Angiotensin II (AII) in 1-10 nM concentrations has an in vivo immunostimulating effect on human neutrophils. The release of superoxide anions and leukotrienes (LTs) is significantly increased by 10 nM AII-stimulated neutrophils of patients with hypercholesterolaemia (HCH). These oxidizing agents may be involved in the damage of vessel walls, i.e., in atherosclerotic plaque formation. To clarify the receptor types and signal pathways in neutrophils of healthy controls and patients, inositol trisphosphate (IP(3)) production and Ca(2+) signalling were studied. Neutrophils were pretreated before AII stimulation with different inhibitory drugs. In control cells, the stimulation occurred predominantly through pertussis toxin-sensitive, type angiotensin 1 receptors. This induced IP(3) production and Ca(2+) signalling from intracellular pools. In neutrophils of hypercholesterolaemic patients, the enhanced release of oxidizing agents was dependent more on type angiotensin 2 than type angiotensin 1 receptors. After stimulation, there was no IP(3) production detected. The Ca(2+) signalling was lower than in control cells and was dependent on extracellular Ca(2+).
authors.affiliation: First Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen H-4012, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Paragh
authors.forename: Jenõ
authors.initials: J
authors.lastname: Szabó
authors.forename: Eva
authors.initials: E
authors.lastname: Kovács
authors.forename: Tamás
authors.initials: T
authors.lastname: Keresztes
authors.forename: István
authors.initials: I
authors.lastname: Kárpáti
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Balogh
authors.forename: Dénes
authors.initials: D
authors.lastname: Páll
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fóris
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D020013:Calcium Signaling; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006937:Hypercholesterolemia / Q000276:immunology* / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D037342:Pertussis Toxin / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000502:physiology; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism
chemical_list: D015289:Leukotrienes; D011945:Receptors, Angiotensin; D013481:Superoxides; D000804:Angiotensin II; D015544:Inositol 1,4,5-Trisphosphate; D037342:Pertussis Toxin