Human serum amyloid A has cytokine-like properties.
Human serum amyloid A (SAA) proteins are a group of 12-14 kDa apolipoproteins found predominantly in the high-density lipoprotein (HDL) fraction of plasma. Several functions have been proposed for SAA, but its primary physiological function remains elusive. In this report, we used the monocytic cell line THP-1 to investigate whether recombinant SAA1 (rSAA) or the HDL-rSAA protein complex can affect the capacity of these cells to produce inflammatory cytokines in vitro. Incubation of rSAA, plasma HDL (which contains < or = 30 microg/ml of SAA) or HDL-rSAA complex with THP-1 cells induced synthesis of IL-1beta, IL-1ra and sTNFR-II protein and mRNA. The induction of cytokine synthesis was not due to endotoxin contamination since the effect was abrogated by protein denaturation. The rSAA and HDL-rSAA complex did not induce detectable levels of IL-6 or TNFalpha protein or mRNA. In contrast 10 microg/ml LPS stimulated secretion of the inflammatory cytokines, IL-1beta, IL-6 and TNFalpha, as well as IL-1ra and sTNFR-II from THP-1 cells. We confirmed that rSAA has chemoattractant properties in vivo, by subcutaneous injections into mice and examined the histology of the injection site at 72 h, however, the HDL-rSAA complex has a substantially reduced effect.
Patel
H
H
Department of Molecular Pathology, University College London Medical School, UK.
Fellowes
R
R
Coade
S
S
Woo
P
P
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000378:metabolism* / Q000494:pharmacology*
D016207:Cytokines; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein