Enteric microflora contribute to constitutive ICAM-1 expression on vascular endothelial cells

Quantitative estimates of endothelial cell adhesion molecule expression have revealed that some adhesion molecules [e.g., intercellular adhesion molecule-1 (ICAM-1)] are abundantly expressed in different vascular beds under normal conditions. The objective of this study was to determine whether the enteric microflora contribute to the constitutive expression of ICAM-1 and other endothelial cell adhesion molecules in the gastrointestinal tract and other regional vascular beds. The dual radiolabeled monoclonal antibody technique was used to measure endothelial expression of ICAM-1, ICAM-2, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in conventional, germ-free mice and germ-free mice receiving the cecal contents of conventional mice to reestablish the enteric microflora (total association). Constitutive ICAM-1 expression was significantly lower in the splanchnic organs (pancreas, stomach, small and large intestine, mesentery, and liver), kidneys, skeletal muscle, and skin of germ-free mice compared with their conventional counterparts. These differences were abolished after total association of germ-free mice with the indigenous gastrointestinal flora. The expression of ICAM-2, VCAM-1, and E-selectin in the various tissues studied did not differ between conventional and germ-free mice. These findings indicate that the indigenous gastrointestinal microflora are responsible for a significant proportion of the basal ICAM-1 expression detected in both intestinal and extraintestinal tissues.

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Anti-inflammatory drugs and endothelial cell adhesion molecule expression in murine vascular beds

Gut ◽

10.1136/gut.44.2.186 ◽

1999 ◽

Vol 44 (2) ◽

pp. 186-195 ◽

Cited By ~ 29

Author(s):

N Mori ◽

Y Horie ◽

M E Gerritsen ◽

D C Anderson ◽

D N Granger

Keyword(s):

Cell Adhesion ◽

Endothelial Cell ◽

Adhesion Molecules ◽

Adhesion Molecule ◽

Distal Colon ◽

Intercellular Adhesion Molecule ◽

Aminosalicylic Acid ◽

Antibody Technique ◽

Vascular Beds ◽

Endothelial Cell Adhesion

BackgroundInflammatory bowel diseases (IBD) are characterised by an intense infiltration of leucocytes that is mediated by adhesion molecules expressed on the surface of activated endothelial cells.AimsTo determine whether drugs used in the treatment of IBD, specifically dexamethasone (DEX), 5-aminosalicylic acid (5-ASA), methotrexate (MTX), and 6-mercaptopurine (6-MP), alter the expression of endothelial cell adhesion molecules (ECAMs).MethodsThe expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular CAM 1 (VCAM-1) in different vascular beds of C57Bl/6J mice was measured using the dual radiolabelled monoclonal antibody technique.ResultsLipopolysaccharide (LPS) elicited a profound increase in the expression of all ECAMs in the mesentery, small intestine, caecum, and distal colon. The LPS induced increase in CAM expression was not significantly affected by prior treatment with either MTX or 6-MP. However, pretreatment with either DEX or 5-ASA significantly attenuated LPS induced increases in expression of P- and E-selectin, and VCAM-1 in the majority of tissues evaluated. DEX also blunted the LPS induced increase in ICAM-1 expression in the caecum and distal colon. DEX, but not 5-ASA, largely abolished the rise in plasma tumour necrosis factor α elicited by LPS.ConclusionsThese findings suggest that DEX and 5-ASA may exert their beneficial therapeutic action in IBD, at least in part, by inhibiting the expression of ECAMs which mediate leucocyte adhesion and transmigration in the microvasculature.

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Novel Cytokine-independent Induction of Endothelial Adhesion Molecules Regulated by Platelet/Endothelial Cell Adhesion Molecule (CD31)

The Journal of Cell Biology ◽

10.1083/jcb.139.1.219 ◽

1997 ◽

Vol 139 (1) ◽

pp. 219-228 ◽

Cited By ~ 46

Author(s):

Marek Litwin ◽

Katherine Clark ◽

Leanne Noack ◽

Jill Furze ◽

Michael Berndt ◽

...

Keyword(s):

Cell Adhesion ◽

Endothelial Cell ◽

Adhesion Molecules ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Endothelial Cell Adhesion Molecule ◽

L Cells ◽

Platelet Endothelial Cell Adhesion ◽

Cell Adhesion Molecule 1 ◽

Endothelial Cell Adhesion

Tumor necrosis factor–α, interleukin-1, and endotoxin stimulate the expression of vascular endothelial cell (EC) adhesion molecules. Here we describe a novel pathway of adhesion molecule induction that is independent of exogenous factors, but which is dependent on integrin signaling and cell–cell interactions. Cells plated onto gelatin, fibronectin, collagen or fibrinogen, or anti-integrin antibodies, expressed increased amounts of E-selectin, vascular cell adhesion molecule–1, and intercellular adhesion molecule–1. In contrast, ECs failed to express E-selectin when plated on poly-l-lysine or when plated on fibrinogen in the presence of attachment-inhibiting, cyclic Arg-Gly-Asp peptides. The duration and magnitude of adhesion molecule expression was dependent on EC density. Induction of E-selectin on ECs plated at confluent density was transient and returned to basal levels by 15 h after plating when only 7 ± 2% (n = 5) of cells were positive. In contrast, cells plated at low density displayed a 17-fold greater expression of E-selectin than did high density ECs with 57 ± 4% (n = 5) positive for E-selectin expression 15 h after plating, and significant expression still evident 72 h after plating. The confluency-dependent inhibition of expression of E-selectin was at least partly mediated through the cell junctional protein, platelet/endothelial cell adhesion molecule–1 (PECAM-1). Antibodies against PECAM-1, but not against VE-cadherin, increased E-selectin expression on confluent ECs. Co– culture of subconfluent ECs with PECAM-1– coated beads or with L cells transfected with full-length PECAM-1 or with a cytoplasmic truncation PECAM-1 mutant, inhibited E-selectin expression. In contrast, untransfected L cells or L cells transfected with an adhesion-defective domain 2 deletion PECAM-1 mutant failed to regulate E-selectin expression. In an in vitro model of wounding the wound front displayed an increase in the number of E-selectin–expressing cells, and also an increase in the intensity of expression of E-selectin positive cells compared to the nonwounded monolayer. Thus we propose that the EC junction, and in particular, the junctional molecule PECAM-1, is a powerful regulator of endothelial adhesiveness.

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Endothelial cell adhesion molecule (ECAM) expression in germ-free and conventionalized interleukin-10 deficient mice

Gastroenterology ◽

10.1016/s0016-5085(00)83485-x ◽

2000 ◽

Vol 118 (4) ◽

pp. A346

Author(s):

Shigeyuki Kawachi ◽

Henri C. Van Der Heyde ◽

Laura Gray ◽

Edward Balish ◽

Matthew B. Grisham

Keyword(s):

Cell Adhesion ◽

Endothelial Cell ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Interleukin 10 ◽

Germ Free ◽

Endothelial Cell Adhesion Molecule ◽

Deficient Mice ◽

Endothelial Cell Adhesion

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Role of superoxide in hemorrhagic shock-induced P-selectin expression

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.2.h791 ◽

2000 ◽

Vol 279 (2) ◽

pp. H791-H797 ◽

Cited By ~ 51

Author(s):

Feza M. Akgür ◽

Mark F. Brown ◽

Gazi B. Zibari ◽

John C. McDonald ◽

Charles J. Epstein ◽

...

Keyword(s):

Cell Adhesion ◽

Endothelial Cell ◽

Nadph Oxidase ◽

Xanthine Oxidase ◽

Adhesion Molecule ◽

Oxygen Radicals ◽

Whole Body ◽

Antibody Technique ◽

Vascular Beds ◽

Endothelial Cell Adhesion

Superoxide has been implicated in the regulation of endothelial cell adhesion molecule expression and the subsequent initiation of leukocyte-endothelial cell adhesion in different experimental models of inflammation. The objective of this study was to assess the contribution of oxygen radicals to P-selectin expression in a murine model of whole body ischemia-reperfusion, i.e., hemorrhage-resuscitation (H/R), with the use of different strategies that interfere with either the production (allopurinol, CD11/CD18-deficient or p47phox−/− mice) or accumulation [intravenous superoxide dismutase (SOD), mutant mice that overexpress SOD] of oxygen radicals. P-selectin expression was quantified in different regional vascular beds by use of the dual-radiolabeled monoclonal antibody technique. H/R elicited a significant increase in P-selectin expression in all vascular beds. This response was blunted in SOD transgenic mice and in wild-type mice receiving either intravenous SOD or the xanthine oxidase inhibitor allopurinol. Mice genetically deficient in either a subunit of NADPH oxidase or the leukocyte adhesion molecule CD11/CD18 also exhibited a reduced P-selectin expression. These results implicate superoxide, derived from both xanthine oxidase and NADPH oxidase, as mediators of the increased P-selectin expression observed in different regional vascular beds exposed to hemorrhage and retransfusion.

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Quantification of murine endothelial cell adhesion molecules in solid tumors

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.277.3.h1156 ◽

1999 ◽

Vol 277 (3) ◽

pp. H1156-H1166 ◽

Cited By ~ 4

Author(s):

Robert R. Langley ◽

Janice Russell ◽

Michael J. Eppihimer ◽

Steven J. Alexander ◽

Mary Gerritsen ◽

...

Keyword(s):

Cell Adhesion ◽

Endothelial Cell ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Tumor Bearing ◽

Tnf Α ◽

Endothelial Cell Adhesion Molecules ◽

Vascular Beds ◽

Cell Adhesion Molecule 1 ◽

Endothelial Cell Adhesion

Coordinated adhesive interactions between lymphocyte receptors and endothelial cell adhesion molecules (CAMs) are a prerequisite for effector cell entry into tumor stroma. Whereas the diminished leukocyte-endothelial cell interactions observed in tumor microvessels have been attributed to a reduced expression of endothelial CAMs, there is no quantitative data bearing on this issue. The dual-radiolabeled monoclonal antibody technique was used to quantify constitutive and tumor necrosis factor (TNF)-α-induced expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), ICAM-2, P-selectin, E-selectin, and platelet-endothelial cell adhesion molecule 1 (PECAM-1) in different vascular beds of normal (C57Bl/6) and RM-1 tumor-bearing mice. When corrected for endothelial surface area, the constitutive expression of selectins in tumor vessels was higher than that observed in other vascular beds. Both constitutive and induced expression of endothelial CAMs in peripheral vascular beds did not differ between normal and tumor-bearing mice. Within the tumor, the magnitude of the upregulation of P-selectin, ICAM-1, and VCAM-1 after TNF-α was similar to that within other vascular beds. E-selectin expression in tumors was refractory to TNF-α, whereas PECAM-1 and ICAM-2 expression were significantly reduced. Our findings suggest that the presence of a solid tumor does not influence endothelial CAM expression in other vascular beds and that the higher density of selectins in nonstimulated tumor vessels may promote the recruitment of rolling leukocytes in this tissue.

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