HUMAN SERUM AMYLOID-A HAS CYTOKINE-LIKE PROPERTIES

Human serum amyloid A (SAA) proteins are a group of 12-14 kDa apolipop roteins found predominantly in the high-density lipoprotein (HDL) frac tion of plasma. Several functions have been proposed for SAA, but its primary physiological function remains elusive. In this report, we use d the monocytic cell line THP-1 to investigate whether recombinant SAA 1 (rSAA) or the HDL-rSAA protein complex can affect the capacity of th ese cells to produce inflammatory cytokines in vitro. Incubation of rS AA, plasma HDL (which contains less than or equal to 30 mu g/ml of SAA ) or HDL-rSAA complex with THP-I cells induced synthesis of IL-1 beta, IL-1ra and sTNFR-II protein and mRNA. The induction of cytokine synth esis was not due to endotoxin contamination since the effect was abrog ated by protein denaturation. The rSAA and HDL-rSAA complex did not in duce detectable levels of IL-6 or TNF alpha protein or mRNA. In contra st 10 mu g/ml LPS stimulated secretion of the inflammatory cytokines, IL-1 beta, IL-6 and TNF alpha, as well as IL-1ra and sTNFR-II from THP -1 cells. We confirmed that rSAA has chemoattractant properties in viv o, by subcutaneous injections into mice: and examined the histology of the injection site at 72 h, however, the HDL-rSAA complex has a subst antially reduced effect.