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

FEBS Letters
E MalleW Sattler

Abstract

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 microM) stimulated cells SAA1 led to a pronounced dose-dependent increase of TXA2, PGE2, and PGF2alpha. 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-Gys51 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.

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Citations

Oct 3, 1999·European Journal of Biochemistry·C M Uhlar, A S Whitehead
Jul 26, 2011·Veterinary Immunology and Immunopathology·Lise C BergStine Jacobsen
Jan 22, 2005·Veterinary Immunology and Immunopathology·S JacobsenE Gruys
Dec 13, 2005·Veterinary Immunology and Immunopathology·Stine JacobsenPia Haubro Andersen
Dec 3, 2003·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Golnar KamalvandZafer Ali-Khan
Jan 19, 2018·Equine Veterinary Journal·D SchwartzM M Christopher
Mar 11, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·A ArtlE Malle
Jul 24, 2020·British Journal of Pharmacology·Calum T RobbChengcan Yao
Jan 24, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hong CaiCarolyn L Geczy

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