Low density lipoprotein inhibits the physical interaction of phlogistic crystals and inflammatory cells

Low density lipoprotein (LDL) is the major plasma inhibitor of neutrophil oxidative and lytic responses to monosodium urate crystals and may function to modulate acute gouty inflammation. LDL inhibited apparent phagocytosis of urate crystals by human neutrophils, suggesting it may interfere with early events in the crystal-induced stimulation of neutrophils. The effects were not specific for neutrophils, since human platelet secretory and membranolytic responses to urate crystals were also inhibited by purified LDL in doses as low as 10 micrograms/ml. As with neutrophils, the inhibitory activity of LDL was stimulus-specific. Since LDL binds to urate crystals and specifically inhibits a range of cellular responses to them, including phagocytosis, we hypothesized that LDL interferes with the initial crystal-cell interaction. We measured platelet interaction with urate crystals and found that LDL was a potent inhibitor of crystal-induced platelet sedimentation and was 10-100-fold more active than lipoprotein-depleted plasma or purified high density lipoprotein. In summary, LDL inhibits a broad range of responses of a number of inflammatory cell types to certain inflammatory surfaces, and this effect appears to be due to inhibition of physical association of crystals with cell membranes.