Extended Data Fig. 8: The protective effects on thrombosis, vascular injury and inflammation are specific to ANGPTL4 and rely on the binding motif (aa 66-80) in its N-terminus ___domain.
From: Angiopoietin-like 4 protects against endothelial dysfunction during bacterial sepsis
a-f, SCID mice grafted with human skins were infected intravenously with N. meningitidis 2C4.3 (5 × 106 bacteria) or received vehicle. A period of 30 min after bacterial challenge, (b-d) mice received 1 µg of recombinant human ANGPTL3 or ANGPTL8 intravenously or the vehicle as a control (n = 3 mice per group); e,f, mice received 1 µg of nANGPTL4, Peptides P1, P9 or P10 intravenously or the vehicle as a control (n = 3 mice per group and this experiment was performed twice with n = 3 mice per group, for nANGPTL4 and P1 using skin from two different donors). Mice were killed at 4 h post-challenge. a, A schematic representation of the protocols used in vivo. b,e, Bacterial colonization and c,f, Thrombus formation within the skin grafts were assessed by immunofluorescence analysis and quantified as described in Fig. 3. Error bars show mean ± s.e.m.; 10 to 60 vessels per mouse were analysed; One-way ANOVA Tukey’s multiple comparison test, *** P < 0.001; NS, not significant (NS1 > 0.9999, NS2 = 0.264, NS3 = 0.9151, NS4 = 0.6748, NS5 = 0.7817). d, Production of human cytokines (IL-6 and IL-8) and markers of vascular inflammation (E-selectin, ICAM-1, VCAM-1) in the mouse plasma was quantified with multiplex electrochemiluminescent immunoassays: one point corresponds to one mouse. Error bars show the mean ± s.e.m. from one representative experiment; Ordinary one-way ANOVA Dunnett’s multiple comparison test. *P < 0.05; **P < 0.01; NS, not significant (NS1 = 0.3605, NS2 = 0.9183, NS3 = 0.089, NS4 = 0.6388, NS5 = 0.9434, NS6 = 0.9999, NS7 = 0.4262, NS8 = 0.9828, NS9 = 0.1948, NS10 = 0.6607, NS11 = 0.3228, NS12 = 0.2243).
