VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis

doi:10.1016/S0016-5085(99)70070-3

Gastroenterology

Volume 116, Issue 4, April 1999, Pages 874-883

https://doi.org/10.1016/S0016-5085(99)70070-3 Get rights and content

Abstract

Background & Aims: The molecular mechanisms responsible for leukocyte recruitment in experimental colitis are poorly understood. The aims of this study were to measure expression of endothelial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and to determine their role in leukocyte recruitment in experimental colitis. Methods: Rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis and control rats were studied 1, 7, or 21 days after treatment. ICAM-1 and VCAM-1 expressions were measured by the double radiolabeled antibody technique. Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. Therapeutic effects of treatment with anti–VCAM-1 antibodies were also assessed. Results: Colonic endothelial ICAM-1 was constitutively expressed and did not increase in colitic animals. In contrast, constitutive expression of VCAM-1 was low but markedly increased (6-fold) 1 and 7 days after induction of colitis. Increased colonic expression of VCAM-1 paralleled macroscopic damage score, myeloperoxidase activity, and increased leukocyte adhesion in colonic venules. The latter was significantly decreased by immunoneutralization of ICAM-1 and completely abrogated by immunoneutralization of VCAM-1. Long-term administration of anti–VCAM-1 antibody resulted in significant attenuation of colitis. Conclusions: Induction of colitis in rats by TNBS is followed by up-regulation of endothelial VCAM-1. VCAM-1 and constitutive ICAM-1 are major determinants of leukocyte recruitment to the inflamed intestine.

GASTROENTEROLOGY 1999;116:874-883

Section snippets

Induction of colitis

Male Sprague–Dawley rats weighing 275–325 g were obtained from Charles River (Saint Aubin les Elbeuf, France). Colitis was induced by intracolonic administration of 30 mg of TNBS (Sigma Química, Madrid, Spain) in 0.25 mL of 50% (vol/vol) ethanol (Merck, Darmstadt, Germany).¹ Additional groups of animals were treated with 0.25 mL of 50% ethanol, and control rats received 0.25 mL of saline. Principles of laboratory animal care (NIH publication no. 86-23, revised 1985) and the guidelines of

Study 1: Characterization of macroscopic changes, histology, and MPO activity

Quantification of macroscopic and histological changes, distal colon weight, and MPO activity are summarized in Table 1.

. Macroscopic and histological changes, colon weight, and MPO activity of control and ethanol- and TNBS-treated rats

Group	Macroscopic score	Microscopic score	Colon weight (g)	MPO activity (U/g)
Saline	0 ± 0	0 ± 0	0.57 ± 0.05	0.97 ± 0.23
Ethanol 1 day	0.75 ± 0.25	4.25 ± 1.37^a	0.78 ± 0.05	2.27 ± 0.65
Ethanol 7 days	0.25 ± 0.25	2.75 ± 0.25	0.62 ± 0.05	1.82 ± 0.48
Ethanol 21 days	0.25 ± 0.25	1.75 ± 0.75

Discussion

This study suggests that VCAM-1 plays a central role in the recruitment of leukocytes in TNBS-induced colitis in rats and underscores important discrepancies in the pattern of expression of this adhesion molecule and ICAM-1. Characterization of VCAM-1 expression and functional significance in a rat model of colitis has not been possible until recently because of unavailability of MAbs. Previous studies assessing activation of VCAM-1 in IBD have given conflicting results influenced by the

References (46)

GP Morris et al.
Hapten-induced model of chronic inflammation and ulceration in the rat colon
Gastroenterology
(1989)
CO Elson et al.
Experimental models of inflammatory bowel disease
Gastroenterology
(1995)
PG Norris et al.
Adhesion molecule expression in polymorphic light eruption
J Invest Dermatol
(1992)
D Wong et al.
Expression of vascular cell adhesion molecule-1 (VCAM-1) by human brain microvessel endothelial cells in primary culture
Microvasc Res
(1995)
M Mourelle et al.
Polyunsaturated phosphatidylcholine prevents stricture formation in a rat model of colitis
Gastroenterology
(1996)
PP Bradley et al.
Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker
J Invest Dermatol
(1982)
MJ Sanz et al.
Tumor necrosis factor alpha–induced eosinophil accumulation in rat skin is dependent on alpha4 integrin/vascular cell adhesion molecule-1 adhesion pathways
Blood
(1997)
L Ma et al.
A sialoglycoprotein from human leukocytes functions as a ligand for P-selectin
J Biol Chem
(1994)
J Panés et al.
Portal hypertension enhances endotoxin-induced intercellular adhesion molecule 1 up-regulation in the rat
Gastroenterology
(1996)
S Komatsu et al.
Effects of intestinal stasis on intercellular adhesion molecule 1 expression in the rat: role of enteric bacteria
Gastroenterology
(1997)

U Henseleit et al.

Expression of murine VCAM-1 in vitro and in different models of inflammation in vivo: correlation with immigration of monocytes

Exp Dermatol

(1994)

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^☆: Address requests for reprints to: Julián Panés, M.D., Department of Gastroenterology, Hospital Clínic, Villaroel 170, 08036 Barcelona, Spain. e-mail: [email protected]; fax: (34) 93-4515272.

^☆☆: Supported by grant SAF97-0040 from Comisión Interministerial de Ciencia y Tecnología. Dr. M. Sans is a recipient of a grant from Hospital Clínic and from Fundació Universitària Agustí Pedro Pons.

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Alimentary TractVCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis☆,☆☆

Abstract

Section snippets

Induction of colitis

Study 1: Characterization of macroscopic changes, histology, and MPO activity

Discussion

Gastroenterology

Gastroenterology

J Invest Dermatol

Microvasc Res

Gastroenterology

J Invest Dermatol

Blood

J Biol Chem

Gastroenterology

Gastroenterology

Microvasc Res

Gastroenterology

Blood

Gastroenterology

Cell

Gastroenterology

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A comparative analysis of two models of colitis in rats

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Induction of ICAM-1 by TNF-alpha, IL-1 beta, and LPS in human endothelial cells after downregulation of PKC

Am J Physiol

Expression of murine VCAM-1 in vitro and in different models of inflammation in vivo: correlation with immigration of monocytes

Exp Dermatol

Alimentary Tract
VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis☆,☆☆