Apolipoprotein B mediates the capacity of low density lipoprotein to suppress neutrophil stimulation by particulates.
Low density lipoprotein (LDL) inhibits phagocytosis of certain negatively charged particulates and also inhibits subsequent cellular secretory and oxidative responses to these particulates. In the present work, we have defined the structural features of LDL involved in this activity. Starch-heptane extraction depleted greater than 95% of neutral lipids but had little effect on the capacity of LDL to inhibit monosodium urate crystal- or polystyrene latex bead-induced neutrophil chemiluminescence (CL). Liposomes containing gamma-palmitoyl-beta-oleoylphosphatidylcholine (PC) with unesterified cholesterol (PC:cholesterol = 2:1), PC and sphingomyelin (PC:sphingomyelin = 2.3:1), or PC alone lacked the capacity to inhibit urate-induced CL. However, incorporation of apoB-100 into liposomes via cholate dialysis rendered them nearly as inhibitory for urate-induced neutrophil CL as LDL on a protein weight basis. Moreover, delipidated apoB-100, containing less than 3% residual phospholipid, inhibited neutrophil responses to urate crystals or latex beads (degranulation and superoxide anion release) in a stimulus-specific manner. Modifications of the lysine residues of apoB (e.g. acetylation) reduced both the capacity of LDL to inhibit urate crystal-induced CL and to bind to urate crystals. The effects of apoB lysine residue modification were reversible, proportional to the extent of modification, and were not attributable to alteration of the net charge of apoB. Thus, the apoB-100 of LDL both mediates and shares the capacity of native LDL to inhibit certain neutrophil responses to particulates.
D001055:Apolipoproteins B / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008081:Liposomes / Q000494:pharmacology; D008163:Luminescent Measurements; D008239:Lysine; D008854:Microscopy, Electron; D008863:Microspheres; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010743:Phospholipids / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014527:Uric Acid / Q000494:pharmacology
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D008081:Liposomes; D010743:Phospholipids; D014527:Uric Acid; D008239:Lysine