Changes in High Density Lipoprotein Content Following Endotoxin Administration in the Mouse. Formation of Serum Amyloid Protein-rich Subfractions

Bacterial endotoxin is a potent inducer of the serum amyloid protein (apo-SAA), a high density lipoprotein (HDL) apoprotein. In a study of the induction of apo-SAA and the structure of apo-SAA-rich lipoprotein particles in mice, we have observed that, following intraperitoneal administration of Salmonella typhosa lipopolysaccharide (50 micrograms), plasma apo-SAA levels rose from base-line levels of less than 1% to greater than 20% of the HDL protein content at 20 h postinjection. No changes in the relative content of other HDL apoproteins were noted; analysis of apo-SAA-rich HDL lipid content indicated a significant decrease (10%) in phospholipid content relative to that of control HDL. Two major apo-SAA isotypes, apo-SAA1 and apo-SAA2, were identified, having apparent molecular weights of 12,600 and 11,800, respectively, and isoelectric points of 6.35 and 6.20, respectively. Quantitative immunoprecipitation experiments indicated that essentially all of the apo-SAA was bound to lipoprotein particles containing apo-A-I. Apo-SAA was distributed among higher density HDL subfractions than were other HDL apoproteins following density gradient centrifugation, and subfractions having apo-SAA:apo-A-I molar ratios of greater than 2:1 were identified. These results indicate the formation of a subset of apo-SAA-rich HDL particles following apo-SAA induction by endotoxin.