Ensari A, Ager A, Marsh M N, Morgan S, Moriarty K J
University Department of Medicine, University of Manchester School of Medicine, Hope Hospital, UK.
Clin Exp Immunol. 1993 May;92(2):303-7. doi: 10.1111/j.1365-2249.1993.tb03396.x.
Adhesive interactions between endothelium and circulating cells, such as monocytes, neutrophils and lymphocytes, are crucial for localizing the inflammatory response. We investigated the inflammatory response of rectal mucosa to local gluten challenge as a dynamic model of antigen-induced tissue injury, during which the expression of adhesion molecules on leucocytes and endothelial cells could be sequentially observed. Expression of ELAM-1, ICAM-1 and VCAM-1 was monitored in 10 treated and eight untreated patients with gluten sensitivity (coeliac disease), and in five disease controls for up to 4 h (short challenge), while a further seven treated coeliacs were monitored for up to 24 h (long challenge) following rectal gluten challenge. In the former, the expression of VCAM-1 and ELAM-1 was significantly raised 4 h after gluten challenge compared with controls. VCAM-1 and ELAM-1 expression was also increased in mucosae of treated patients, but to a lesser extent. VCAM-1 expression continued to increase for up to 24 h after gluten, while ELAM-1 had begun to wane by 4 h, reaching basal levels by 24 h. In contrast, the expression of ICAM-1 did not change in any of the disease groups studied. These findings relate to significant increases in lymphocytes (CD3+ cells) after 8 h, and neutrophils (CD15+ cells) after 4 h in the lamina propria. This approach has permitted novel studies of the inflammatory response to a defined antigen in sensitized (gluten-sensitive) human patients.
内皮细胞与循环细胞(如单核细胞、中性粒细胞和淋巴细胞)之间的黏附相互作用对于炎症反应的定位至关重要。我们研究了直肠黏膜对局部麸质激发的炎症反应,以此作为抗原诱导组织损伤的动态模型,在此过程中可以依次观察白细胞和内皮细胞上黏附分子的表达。对10例接受治疗和8例未接受治疗的麸质敏感患者(乳糜泻)以及5例疾病对照者进行长达4小时(短期激发)的监测,观察ELAM-1、ICAM-1和VCAM-1的表达情况,同时对另外7例接受治疗的乳糜泻患者在直肠麸质激发后进行长达24小时(长期激发)的监测。在短期激发组中,与对照组相比,麸质激发后4小时VCAM-1和ELAM-1的表达显著升高。在接受治疗患者的黏膜中,VCAM-1和ELAM-1的表达也有所增加,但程度较轻。麸质激发后,VCAM-1的表达持续增加长达24小时,而ELAM-1在4小时时开始下降,到24小时时达到基础水平。相比之下,在所研究的任何疾病组中,ICAM-1的表达均未发生变化。这些发现与固有层中8小时后淋巴细胞(CD3+细胞)和4小时后中性粒细胞(CD15+细胞)的显著增加有关。这种方法使得对致敏(麸质敏感)人类患者对特定抗原的炎症反应进行新的研究成为可能。