Serum amyloid A (SAA) protein enhances formation of cyclooxygenase metabolites of activated human monocytes

FEBS Letters

Gemsa, Diethard⁴  Bollmann, Andreas²  Steinmetz, Armin⁵  Malle, Ernst¹  Sattler, Wolfgang¹  Leis, Hans-Jörg³ 

[1] Karl-Franzens University Graz, Institute of Medical Biochemistry, Harrachgasse 21, A-8010 Graz, Austria;Crozer-Chester Medical Center, Department of Pediatrics, Upland, PA 19013-3995, USA;Karl-Franzens University Graz, Department of Pediatrics, Division of Mass Spectrometry, A-8010 Graz, Austria;Philipps University Marburg, Institute of Immunology, D-35033 Marburg/Lahn, Germany;Philipps University Marburg, Department of Internal Medicine, Division of Endocrinology and Metabolism, D-35033 Marburg/Lahn, Germany

关键词: Acute-phase reaction;    Atherosclerosis;    Calcium-binding property;    Cyclooxygenase;    Eicosanoid;    Gas chromatography/mass spectrometry;    AA;    arachidonic acid;    apo A-I;    apolipoprotein A-I;    HDL;    high density lipoproteins;    NICI-GC/MS;    negative ion chemical ionization-gas chromatography/mass spectrometry;    PGE2;    prostaglandin E2;    PGF2α;    prostaglandin F2α;    PLA2;    phospholipase A2;    PKC;    protein kinase C;    rSAA;    recombinant SAA;    SAA;    serum amyloid A protein;    TXB2;    thromboxane B2;   

DOI  :  10.1016/S0014-5793(97)01459-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

As serum amyloid A (SAA), an apolipoprotein associated with HDL during the acute-phase reaction may induce Ca²⁺ mobilization in human monocytes we raised the question whether SAA₁ the predominant isoform of human acute-phase SAA is able to alter eicosanoid formation. In resting monocytes SAA₁ was without effect on the secretion of cyclooxygenase metabolites while in calcium ionophore A₂₃₁₈₇- (0.5 and 2.5 μM) stimulated cells SAA₁ led to a pronounced dose-dependent increase of TXA₂, PGE₂, and PGF_2α. In addition a time-dependent increase of cyclooxygenase metabolites in between 1.5- and 3-fold in the presence of SAA₁ was observed; apo A-I, the main HDL-apolipoprotein under non-acute-phase conditions, had no effect. Using sequence-specific anti-human SAA₁ peptide (40–63) F(ab)₂ fragments we could show that the proposed Ca²⁺-binding tetrapeptide Gly⁴⁸-Pro⁴⁹-Gly⁵⁰-Gly⁵¹ of SAA₁ is not responsible for enhanced biosynthesis of cyclooxygenase metabolites. Finally, we could demonstrate that human SAA₁ is unable to bind Ca²⁺-ions, suggesting that SAA₁ does not directly enhance eicosanoid biosynthesis via Ca²⁺ mobilization leading to enhanced phospholipase A₂ activity.

【 授权许可】

Unknown