VEGF-A stimulation of leukocyte adhesion to colonic microvascular endothelium: implications for inflammatory bowel disease

Goebel, Stephen; Huang, Meng; Davis, William C.; Jennings, Merilyn H.; Siahaan, Teruna J.; Alexander, J. Steven; Kevil, Christopher G.

doi:10.1152/ajpgi.00466.2005

Cited by 76 publications

(72 citation statements)

References 44 publications

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“…WT and ICAM-1 −/− MAEC were cultured to further examine the manner in which ICAM-1 governs VEGF-A angiogenesis. 50 ng/ml VEGF-A was used for chemotaxis assays as we have previously shown this concentration to be optimal in stimulating ICAM-1 expression and is consistent with pathological levels of VEGF-A in diseased tissue (8). Transwell chemotaxis assays using VEGF-A revealed a significant attenuation of the chemotactic response in ICAM-1 −/− cells compared to WT cells ( Figure 1, panel E).…”

Section: Icam-1 Facilitates Vegf-a Mediated Angiogenesissupporting

confidence: 68%

Regulation of endothelial glutathione by ICAM-1 governs VEGF-A-mediated eNOS activity and angiogenesis

Langston

Chidlow

Booth

et al. 2007

Free Radical Biology and Medicine

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Previous studies suggest that inflammatory cell adhesion molecules may modulate endothelial cell migration and angiogenesis through unknown mechanisms. Using a combination of in vitro and in vivo approaches, herein we reveal a novel redox sensitive mechanism by which ICAM-1 modulates endothelial GSH that controls VEGF-A induced eNOS activity, endothelial chemotaxis, and angiogenesis. In vivo disk angiogenesis assays showed attenuated VEGF-A mediated angiogenesis in ICAM-1 −/− mice. Moreover, VEGF-A dependent chemotaxis, eNOS phosphorylation, and nitric oxide (NO) production were impaired in ICAM-1 −/− MAEC compared to WT MAEC. Decreasing intracellular GSH in ICAM-1 −/− MAEC to levels observed in WT MAEC with 150 μM buthionine sulfoximine (BSO) restored VEGF-A responses. Conversely, GSH supplementation of WT MAEC with 5 mM glutathione ethyl ester (GEE) mimicked defects observed in ICAM-1 −/− cells. Deficient angiogenic responses in ICAM-1 −/− cells were associated with increased expression of the lipid phosphatase, PTEN, consistent with antagonism of signaling pathways leading to eNOS activation. PTEN expression was also sensitive to GSH status, decreasing or increasing in proportion to intracellular GSH concentrations. These data suggest a novel role for ICAM-1 in modulating VEGF-A induced angiogenesis and eNOS activity through regulation of PTEN expression via modulation of intracellular GSH status.

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Section: Icam-1 Facilitates Vegf-a Mediated Angiogenesissupporting

confidence: 68%

Regulation of endothelial glutathione by ICAM-1 governs VEGF-A-mediated eNOS activity and angiogenesis

Langston

Chidlow

Booth

et al. 2007

Free Radical Biology and Medicine

Self Cite

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“…This induction of adhesion molecule expression increases in vitro leukocyte adhesion under static conditions, which occurs through the activation of VEGF-R2 (75,76). Importantly, we have recently reported that VEGF-A stimulates increased ICAM-1 expression on distal colon microvascular endothelium, which facilitates neutrophil and T cell adhesion in a CD18-dependent manner (55). Our group has also shown that ICAM-1 influences control of VEGF-A induced endothelial NO synthase (eNOS) activity, endothelial chemotaxis, and angiogenesis through modulation of endothelial cell signaling pathways (84).…”

Section: Angiogenic Mediators In Ibd and Experimental Colitismentioning

confidence: 88%

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Chidlow

Shukla²,

Grisham³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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139

114

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Chidlow JH Jr, Shukla D, Grisham MB, Kevil CG. Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues. Am J Physiol Gastrointest Liver Physiol 293: G5-G18, 2007. First published April 26, 2007; doi:10.1152/ajpgi.00107.2007.-Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed. inflammation; T cells; growth factors; adhesion molecules; antiangiogenesis ANGIOGENESIS PLAYS AN IMPORTANT role in many chronic inflammatory diseases including but not limited to diabetic retinopathy, atherosclerosis, rheumatoid arthritis, hypercholesterolemia, and psoriasis. It has been suggested that the angiogenic components of these diseases contribute to and exacerbate disease conditions (26, 31). Recent findings, both clinical and experimental, indicate that angiogenesis also plays a crucial role in the inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC) (31,37,58,131,155). Development of new vasculature during chronic inflammation may play a negative "pathological" role by contributing to increased inflammatory responses due to dysfunctional new vessel architecture and increases in the recruitment of inflammatory cell types. Importantly, recent data have shown that angiogenic inhibition during chronic inflammatory diseases attenuates further inflammation and disease pathology (31, 37, 51). As such, expanding our knowledge of how pathological angiogenesis occurs during IBD will further our ability to treat patients with these diseases. IBD PathogenesisCD and UC are idiopathic inflammatory disorders of the intestine and/or colon in which patients suffer from rectal bleeding, severe...

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“…Flow cytometry analysis. Measurement of T-cell and endothelial cell surface adhesion molecule expression was performed by flow cytometry as we have previously reported (20,22,24). Antibodies and the dilutions used against these molecules are as follows: CD18 (1:320), CD29 (1:320), CD11a (1:80), CD49d (1:80), intracellular adhesion molecule-1 (ICAM-1) (1:80), vascular cell adhesion molecule (VCAM-1) (1:80), E-selectin (1:320), and P-selectin (1:320) and isotype controls at the respective dilutions.…”

Section: Methodsmentioning

confidence: 99%

Stromal Cell–Derived Factor-1/CXCL12 Stimulates Chemorepulsion of NOD/LtJ T-Cell Adhesion to Islet Microvascular Endothelium

et al. 2008

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OBJECTIVE—Diabetogenic T-cell recruitment into pancreatic islets faciltates β-cell destruction during autoimmune diabetes, yet specific mechanisms governing this process are poorly understood. The chemokine stromal cell–derived factor-1 (SDF-1) controls T-cell recruitment, and genetic polymorphisms of SDF-1 are associated with early development of type 1 diabetes. RESEARCH DESIGN AND METHODS—Here, we examined the role of SDF-1 regulation of diabetogenic T-cell adhesion to islet microvascular endothelium. Islet microvascular endothelial cell monolayers were activated with tumor necrosis factor-α (TNF-α), subsequently coated with varying concentrations of SDF-1 (1–100 ng/ml), and assayed for T-cell/endothelial cell interactions under physiological flow conditions. RESULTS—TNF-α significantly increased NOD/LtJ T-cell adhesion, which was completely blocked by SDF-1 in a dose-dependent manner, revealing a novel chemorepulsive effect. Conversely, SDF-1 enhanced C57BL/6J T-cell adhesion to TNF-α–activated islet endothelium, demonstrating that SDF-1 augments normal T-cell adhesion. SDF-1 chemorepulsion of NOD/LtJ T-cell adhesion was completely reversed by blocking Giα-protein–coupled receptor activity with pertussis toxin. CXCR4 protein expression was significantly decreased in NOD/LtJ T-cells, and inhibition of CXCR4 activity significantly reversed SDF-1 chemorepulsive effects. Interestingly, SDF-1 treatment significantly abolished T-cell resistance to shear-mediated detachment without altering adhesion molecule expression, thus demonstrating decreased integrin affinity and avidity. CONCLUSIONS—In this study, we have identified a previously unknown novel function of SDF-1 in negatively regulating NOD/LtJ diabetogenic T-cell adhesion, which may be important in regulating diabetogenic T-cell recruitment into islets.

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VEGF-A stimulation of leukocyte adhesion to colonic microvascular endothelium: implications for inflammatory bowel disease

Cited by 76 publications

References 44 publications

Regulation of endothelial glutathione by ICAM-1 governs VEGF-A-mediated eNOS activity and angiogenesis

Regulation of endothelial glutathione by ICAM-1 governs VEGF-A-mediated eNOS activity and angiogenesis

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Stromal Cell–Derived Factor-1/CXCL12 Stimulates Chemorepulsion of NOD/LtJ T-Cell Adhesion to Islet Microvascular Endothelium

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