Serum amyloid A (SAA) is an acute phase reactant whose levels in the blood rise as part of the body's response to stress and inflammation. Previous studies have suggested that SAA may carry an anti-inflammatory potential. We evaluated the effects of SAA on human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine (fMLP) in vitro. At concentrations higher than 10 μg/mL, SAA inhibited neutrophil myeloperoxidase (MPO) release. This effect was located in the N-terminal-that is, amino acid residues 1-14 - of the SAA molecule. Directed neutrophil migration was inhibited at the same SAA concentrations. Several amino acid residues (1 - 14, 15-104, 83-104) contributed to this effect. Neutrophil O2- production was inhibited at low concentrations of SAA (0.1 to 1 μg/ml) and was stimulated at concentrations higher than 50 μg/mL. Neutrophil O2- production induced by phorbol myristate acetate (PMA) and O2- generated by the xanthine-xanthine oxidase reaction were not affected by SAA. These results add to previous data suggesting that SAA, at concentrations recorded in the serum during inflammation, modulates neutrophil function; thus it may play a role in the down-regulation of the inflammatory process.
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N eutrophils are essential components of the host defense dedicated to the destruction of invading pathogens. They are present in large amounts in the circulation and rapidly migrate to tissue on invasion of certain microorganisms. 1 The complex process of their phagocytic action includes, in addition to migration and adhesion, ingestion (phagocytosis), granule enzyme release (degranulation), respiratory From the Hematology Unit, Hadassah University Hospital, Mount Scopus, Jerusalem; and the Department of Organic Chemistry,W eiz-mann Institute of Science, Rehovot. Supported by the Israel Ministry of Absorption and the Israel Cancer Association. Submitted for publication December3 , 1997; revision submittedJ une 25, 1998; acceptedJ une 29, 1998. Reprint requests: Yaacov Matzner, MD, HematologyU nit, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel 91240. Copyright © 1998 by Mosby, Inc. 0022-2143/98 $5.00 + 0 5/1/92789