Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

Figure 1

Structure and characterization of nonbilayer phospholipid arrangements. (a) Representation of a nonbilayer phospholipid arrangement, showing an inverted micelle, with the acyl chains of the phospholipids in a conical arrangement, inserted into the lipid bilayer. (b) Molecular shape of the lipid A of LPS, showing the conical arrangement of its acyl chains. (c to j) Liposomes made of egg-yolk phosphatidylcholine (PC)/egg-yolk phosphatidic acid (PA) (2 : 1 molar ratio), PC/bovine brain phosphatidylserine (PS) (4 : 1) (50 nmol anionic phospholipid in 50 μL TS buffer), or PC alone were incubated at 37°C for 30 min with 2 mM MnCl₂, 1.5 mM chlorpromazine (CPZ), 8 mM procainamide (PCM), 100 ng/mL LPS, 0.1 mM chloroquine (CQ), 0.2 mM MgCl₂, or the indicated mixtures of cations or compounds, respectively. Changes in bilayer complexity (SSc) are represented as histograms: black lines represent liposomes alone or incubated with Mg or PCM + CQ; red lines represent liposomes incubated with Mn or the indicated compound. Values of Kolmogorov-Smirnov test of , , indicate a significant difference between the compared histograms. A representative experiment of five is shown.