Altered signal pathway in angiotensin II-stimulated neutrophils of patients with hypercholesterolaemia.
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+).
Paragh
György
G
First Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen H-4012, Hungary.
Szabó
Jenõ
J
Kovács
Eva
E
Keresztes
Tamás
T
Kárpáti
István
I
Balogh
Zoltán
Z
Páll
Dénes
D
Fóris
Gabriella
G
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
D015289:Leukotrienes; D011945:Receptors, Angiotensin; D013481:Superoxides; D000804:Angiotensin II; D015544:Inositol 1,4,5-Trisphosphate; D037342:Pertussis Toxin