Journal: Journal of immunology (Baltimore, Md. : 1950)

Article Title: Cutting Edge: Lymphatic Vessels, Not Blood Vessels, Primarily Mediate Immune Rejections After Transplantation

doi: 10.4049/jimmunol.0903180

Figure Lengend Snippet: Lymphatic vessels in the recipient bed prior to transplantation determine graft survival. In the 2 wk prior to transplantation (when corneal suture placement was used to induce pathologic corneal neovascularization in the recipient bed), mice were treated with VEGF-TrapR1R2 (a [red line] and c; resulting in no blood or lymphatic vessels, but reduced inflammation in the recipient bed at the time of transplantation), the VEGFR3 Ab mF4-31C1 (a [green line] and d; resulting in no lymphatic vessels, but only blood vessels present in the recipient bed at the time of transplantation), or the JSM6427 integrin α5β1 inhibitor (b [blue line] and e; resulting in no lymphatic vessels, but only blood vessels, present in the recipient bed at the time of transplantation). Graft survival was compared with prehemvascularized and prelymphvascularized controls (a and b [black line], f: “high-risk” recipient bed) and avascular recipient controls (a and b [dotted line], g: “low-risk” recipient bed). The graft survival was significantly better when transplants were placed into recipient beds lacking lymphatic vessels compared with beds with lymphatic vessels present at the time of transplantation (VEGF-Trap versus high-risk: p < 0.0001; VEGFR3 versus high-risk: p < 0.0002; n = 10; JSM6427 versus high-risk: p < 0.032, n = 23; Kaplan–Meyer survival curve). (c–g) Representative images of recipient corneal beds at the time of transplantation after corneas were treated with VEGF-TrapR1R2 (c), mF4-31C1 (VEGFR3 Ab) (d ), JSM6427 (e), or untreated high-risk (f ) and normal-risk (g) recipient beds (original magnification ×100). Green, blood vessels; red, lymphatic vessels; arrow, prevascularized cornea.

Article Snippet: Integrin inhibitor JSM6427: mice in this treatment group ( n = 23) received integrin α5β1 inhibiting molecules [JSM6427; developed and provided by Jerini AG ( 14 )] or carrier solution of JSM6427 as control ( n = 10) systemically via s.c. osmotic pumps (Alzet pumps, Cupertino, CA), as described previously ( 10 ), for 14 d after suture placement prior to corneal transplantation. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIGURE 1 caption a7 Generation of different transplantation models.

Techniques: Transplantation Assay

Journal: Advanced Science

Article Title: Intratumoral Collagen Deposition Supports Angiogenesis Suggesting Anti‐angiogenic Therapy in Armored and Cold Tumors

doi: 10.1002/advs.202409147

Figure Lengend Snippet: Collagen upregulates SOX18 expression through the integrin α5β1/MEK/ERK signaling pathway. a) Expression levels of collagen receptors across different cell types in the scRNA‐seq dataset, with ITGB1 and ITGA5 showing the highest positive correlation. b) Spatial charting of ITGA5‐B1 and VWF in the P10_T4 LUAD sample from Marco De Zuani et al.’s study, [ ²⁶ ] alongside ITGA5‐B1 expression in endothelial and non‐endothelial cells in the spatial transcriptomic dataset. Statistical significance was determined using the Chi‐square test. *** P < 0.001. c) Expression levels of SOX18, ITGA5, and ITGB1 in tumor cells (A549 and H1299), HUVECs, and CAFs. d) Enhanced co‐localization of ITGA5 and ITGB1 following collagen stimulation. Scale bar = 5 µm. e) Impact of collagen stimulation and ITGA5‐B1 blockade on the MEK/ERK pathway in HUVEC cells. f) Effects of collagen stimulation and MEK/ERK inhibition on SOX18 expression in HUVEC cells. g) Effects of collagen stimulation, ITGA5‐B1 blockade, and MEK/ERK blockade on the subcellular localization of SOX18 in HUVEC cells. Scale bar = 5 µm. Statistical significance was determined using ANOVA with Tukey's multiple‐comparison test. ns, non‐significance, *** P < 0.001. n = 3 per group. h) Effects of collagen stimulation, ITGA5‐B1 blockade, and MEK/ERK blockade on the expression of SOX18 downstream targets, MMP7 and CXCL12, in HUVEC cells. Statistical significance was determined using ANOVA with Tukey's multiple‐comparison test. ** P < 0.01, *** P < 0.001. n = 3 per group. Abbreviations: ITGB1: integrin beta 1; ITGA5: integrin alpha 5; VWF: von‐Willebrand factor; SOX18: sex determining region Y box 18; CAF: cancer‐associated fibroblast.

Article Snippet: The integrin α5β1 inhibitor, ATN‐161, [ ] was obtained from TargetMol (catalog T10397) at a working concentration of 1 µmol L −1 , and the MAPK inhibitor, U0126, [ ] was purchased from TargetMol (catalog T21332) with a working concentration of 5 µmol L −1 for in vitro assays.

Techniques: Expressing, Inhibition, Comparison