Natural cytotoxins in human plasma: isolation and characterization of phospholipids associated with cytotoxic lipoproteins.

Most of the heat-stable natural cytotoxins in normal human plasma were fractionated by gel filtration into two active fractions: the alpha 2-macroglobulin (alpha 2M) and pre-alpha 2M pools. The pre-alpha 2M pool also appeared to contain most of the phospholipids in human plasma. The pre-alpha 2M pool was further purified by ultracentrifugation and was shown to contain cytotoxic lipoproteins that represented most of the cytotoxin activity in the pool. The phospholipids associated with the pre-alpha 2M pool and purified lipoproteins resisted dialysis in a buffered saline but were extractable by organic solvents. Two major phospholipids (compounds A and B) were extracted, and both exhibited cytotoxic activities. Compound A exerted dose-dependent, species-nonspecific growth-inhibitory or cytotoxic effects on tumor cells in vitro. It was a lecithin-like compound but was more potent than any of the lecithin standards tested, except for a polyunsaturated lecithin. The possibilities that certain lecithin-like compound(s) contribute significantly to the cytotoxic activity of the lipoproteins and their role in cancer resistance are discussed.