Fig 2: Schematic representation of ricin-induced vascular damage following i.m. exposure of mice and swine. Following ricin intoxication, the vascular endothelium underwent pathophysiological changes, such as degradation of various components of the glycocalyx (syndecan-1, HS and HA), the release of thrombomodulin and ICAM-1, exposure of VWF to the bloodstream and breakdown of VE-cadherin between adjacent endothelial cells. As a consequence of these events, widespread hemorrhages, coagulopathy, vascular hyperpermeability and eventually microvasculature malfunction were detected. Created with BioRender.com.

Fig 3: Absence of apoA-I increases ICAM-1 protein levels, hippocampal parenchymal ICAM-1 levels, and both cortical and hippocampal endothelial ICAM-1 levels. a Total ICAM-1 protein in soluble half-brain homogenates was measured by ELISA. Confocal microscopy was used to (b) identify co-localization of ICAM-1 with the endothelial cell marker CD31 and (c) evaluate the co-localization of some ICAM-1 in the brain parenchyma with GFAP-positive astrocytes. Total ICAM-1 staining area was visualized by immunofluorescence in cortical (d, e) and hippocampal (f, g) regions and positive staining area was normalized to total region area (h, j, k, m). Vascular-specific and parenchymal ICAM-1 expression was visualized using immunofluorescence and shows association of GFAP with CD31 in (h–j) cortical and (k–m) hippocampal regions, where positive co-stained area was normalized to total CD31-positive area. Representative images for immunofluorescent data are below the graphs. Points represent individual mice, and bars represent mean values. Circles represent female mice, and squares represent male mice. Omnibus analyses of apoA-I and APP/PS1 genotype effects by two-way ANOVA are displayed as exact p values below graphs. Sidak’s multiple comparisons test results are displayed within graphs as *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. For ELISA, N = 6–19 mice per genotype were used. apoA-I, apolipoprotein A-I; HEM, hemizygous apoA-I genotype; KO, knockout apoA-I genotype; WT, wildtype APP/PS1 genotype; APP/PS1, transgenic APP/PS1 genotype; ICAM-1, intercellular adhesion molecule 1; GFAP, glial fibrillary acidic protein; CD31, cluster of differentiation 31. Green closed arrowheads indicate examples of vascular ICAM-1, and white open arrowheads indicate examples of parenchymal ICAM-1

Fig 4: An anti-L1CAM antibody (Ab417) inhibits irradiation (IR)- and Dox-induced vascular DNA damage and perivascular fibrosis with L1CAM nuclear localisation, EndMT and cardiac TnT loss.a–e Mice were injected intravenously with control IgG or Ab417 (10 mg/kg) three times a week for 2 weeks and received 16 Gy thoracic IR (No IR n = 7; IR + IgG n = 8; IR + Ab417 n = 8). f–j Mice were injected intravenously with control IgG or Ab417 (10 mg/kg) with or without intraperitoneal Dox injection (4 mg/kg) three times a week for 2 weeks (No Dox n = 7; Dox+IgG n = 8; Dox+Ab417 n = 8). a, f Immunohistochemical detection (left panels) of L1-CT and ?-H2AX in heart tissues 1 week post IR (a) and 2 weeks after Dox treatment (f). The quantified L1-CT+ cells and ?-H2AX+ cells among ECs are shown (magnification, ×200; right panels). Scale bar = 50 µm. Error bars represent mean ± SEM (L1-CT: IR + IgG vs. IR + Ab417 p = 0.0004, ?-H2AX: No IR vs. IR + IgG p = 0.0076; IR + IgG vs. IR + Ab417 p = 0.0017; Dox + IgG vs. Dox+Ab417 p = 0.0003, **** p < 0.0001). b, g Haematoxylin and eosin staining, Masson’s trichrome staining, and immunohistochemical detection of CD31 in heart tissues (left panels); and quantification of arterial wall thickness, perivascular fibrosis area, and microvessel density per field in heart tissues (magnification, ×200; right panels). Scale bar = 100 µm. The arrow in b indicates inflammatory cell infiltration. Error bars represent mean ± SEM (Arterial wall thickness: No IR vs. IR + IgG p < 0.0001; IR + IgG vs. IR + Ab417 p = 0.0159; No Dox vs. Dox p = 0.0009; Dox + IgG vs. Dox + Ab417 p = 0.0117, perivascular fibrosis area: No IR vs. IR + IgG p = 0.0011; IR + IgG vs. IR + Ab417 p = 0.0168; No Dox vs. Dox p = 0.0001; Dox + IgG vs. Dox + Ab417 p = 0.0492, MVD: No IR vs. IR + IgG p = 0.0012; IR + IgG vs. IR + Ab417 p = 0.0184; No Dox vs. Dox p = 0.0093; Dox + IgG vs. Dox + Ab417 p = 0.0378). c, h Serum CRP, E-selectin, and ICAM-1 levels 1 week post IR (c) and 1 week after Dox treatment (h). Error bars represent mean ± SD (CRP: No IR vs. IR + IgG p < 0.0001; IR + IgG vs. IR + Ab417 p = 0.0015; No Dox vs. Dox p = 0.0007; Dox+IgG vs. Dox+Ab417 p = 0.0003, E-selectin: No IR vs. IR + IgG p = 0.0031; IR + IgG vs. IR + Ab417 p = 0.02; No Dox vs. Dox p = 0.0003; Dox+IgG vs. Dox+Ab417 p = 0.0082, ICAM-1: No IR vs. IR + IgG p = 0.0053; IR + IgG vs. IR + Ab417 p = 0.01; No Dox vs. Dox p = 0.0154). d, i Immunofluorescence detection (upper panel) of L1-CT and CD31 in mouse heart tissues 1 week post IR (d) and 2 weeks after Dox treatment (i) (magnification, ×400). Scale bar = 5 µm. Quantification of L1CAM in CD31 nuclei (lower panel). Error bars represent mean ± SEM (No IR vs. IR + IgG p = 0.0012; IR + IgG vs. IR + Ab417 p = 0.0033; No Dox vs. Dox p < 0.0001; Dox IgG vs. Dox+Ab417 p = 0.0004). e, j Immunofluorescence staining of a-SMA and CD31 (scale bar = 10 µm) and of WGA and cTnT (scale bar = 20 µm) in heart tissues 1 week post IR (e) and 2 weeks post Dox treatment (j) (magnification, ×400; upper panels). Quantification of the a-SMA+CD31+ area in the CD31+ area and quantification of the cTnT area per field (lower panels). Error bars represent mean ± SEM (SMA+CD31+ area in the CD31+ area: No IR vs. IR + IgG p < 0.0001; IR + IgG vs. IR + Ab417 p = 0.0011; No Dox vs. Dox p = 0.0013; Dox + IgG vs. Dox + Ab417 p = 0.0103, cTnT area: No IR vs. IR + IgG p = 0.0019; IR + IgG vs. IR + Ab417 p = 0.0107; No Dox vs. Dox p = 0.0126; Dox + IgG vs. Dox + Ab417 p = 0.0494, one-way ANOVA for multiple comparisons). Data are representative of three independent experiments.

Fig 5: SLURP1 promotes the pathogenesis of E coli K1 meningitis in mice model. (A) Survival curve of C57BL/6 mice treated with SLURP1 (100 mg/kg body weight) + E. coli K1 (1 × 106) or treated with only E coli K1 (1 × 106). SLURP1 was intraperitoneally injected 2 days before E coli K1 challenge. n = 10 per group. (B, C) Pathogen (B) and PMN (C) counts in the CSF of E coli K1-infected mice pretreated with BSA or indicated doses of SLURP1. (D) The OD620 values of Evans blue extracted from the brain of E coli K1-infected mice pretreated with BSA or indicated doses of SLURP1. (E) Representative H&E staining of the cortex sections, scale bar = 200 μm; and (F) meningeal inflammation score. (G–I) The cytokines levels in the CSF were analyzed by ELISA: TNF-α (G), MMP-9 (H), and ICAM-1 (I). The H&E staining are representative of two independent experiments (E). Data are presented as mean ± SEM from two independent experiments. Each dot indicates an individual mouse (n = 5). *p < 0.05; **p < 0.01; ***p < 0.001 by log-rank test (A), Student’s t-test (F), and one-way ANOVA followed by Bonferroni post-hoc test (B–D, G–I). ns, not significant.