Sans M, Panés J, Ardite E, Elizalde J I, Arce Y, Elena M, Palacín A, Fernández-Checa J C, Anderson D C, Lobb R, Piqué J M
Department of Gastroenterology, Institut d'Investigacions Biomédiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
Gastroenterology. 1999 Apr;116(4):874-83. doi: 10.1016/s0016-5085(99)70070-3.
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.
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.
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.
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.
实验性结肠炎中白细胞募集的分子机制尚不清楚。本研究旨在检测内皮细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）的表达，并确定它们在实验性结肠炎白细胞募集中的作用。
研究三硝基苯磺酸（TNBS）诱导的结肠炎大鼠和对照大鼠在治疗后1、7或21天的情况。采用双放射性标记抗体技术检测ICAM-1和VCAM-1的表达。通过荧光活体显微镜观察结肠小静脉中的白细胞-内皮细胞相互作用。还评估了抗VCAM-1抗体治疗的效果。
结肠内皮ICAM-1呈组成性表达，在结肠炎动物中未增加。相比之下，VCAM-1的组成性表达较低，但在结肠炎诱导后1天和7天显著增加（6倍）。结肠VCAM-1表达的增加与宏观损伤评分、髓过氧化物酶活性以及结肠小静脉中白细胞黏附的增加平行。后者通过ICAM-1的免疫中和显著降低，并通过VCAM-1的免疫中和完全消除。长期给予抗VCAM-1抗体导致结肠炎明显减轻。
TNBS诱导大鼠结肠炎后，内皮VCAM-1上调。VCAM-1和组成性ICAM-1是白细胞募集到炎症肠道的主要决定因素。
