The role of ICAM-1 on T-cells in the pathogenesis of asthma

Abstract

The capacity of inflammatory cells to adhere is critical to inflammatory responses and involves an array of adhesion molecules grouped into distinct families. Intercellular adhesion molecule (ICAM)-1 has recently attracted much interest in view of increasing evidence that it plays a prominent role in allergic diseases such as asthma and rhinitis. Apart from its role in adhesion of inflammatory cells to vascular endothelium, the extracellular matrix and epithelium, ICAM-1 mediates T-cell/T-cell, T-cell/target cell and T-cell/B-cell interactions. ICAM-1 on the surface of T-cells is thought to participate in signal transduction and may thus modulate several functions including activation, proliferation, cytotoxicity and cytokine production. Because ICAM-1 is the receptor for the major group of rhinoviruses, the most important cause of acute asthma attacks, binding of rhinovirus (RV) to ICAM-1 on T-cells may, at least theoretically, modulate their function. We review here the role of ICAM-1 in asthma and focus more specifically on its expression on T-cells. We present evidence for a general increase in ICAM-1 expression in this disease including recent observations of enhanced expression on the surface of T-cells in the airways lumen. Whilst the implications of intercellular adhesion molecule- upregulation in asthma remain to be fully elucidated, its participation in cell trafficking and activation are being considered as a target for treatment. We present here early attempts to interfere with intercellular adhesion molecule-1 as an adhesion molecule involved in cell influx and studies aimed preventing virus-induced exacerbations of asthma in children based on the knowledge that intercellular adhesion molecule-1 is the receptor for rhinoviruses.

Differential Contribution of Adhesion Molecules to Th1 and Th2 Cell-Mediated Lung and Bowel Inflammation

“…[21][22][23] The interaction of αL/β2 integrin and ICAM-1 is also a target for the treatment of allergic diseases. 23,24) Eosinophil and T cell infiltration recorded in the lungs of Th2 cell-transferred mice in this study generally supports previous research, but the contribution of α4/β1 was not observed. As the adhesion molecule network is highly redundant (Figs.…”

“…These contradictory findings might be caused by the participation of remaining receptors/ligands, such as ICAM-2, ICAM-3, and αM. 24) Furthermore, we previously showed that a fraction of infused T cells spontaneously distributed in the lungs before antigen provocation rather than those migrated in response to the antigen plays a primary role in the development of lung inflammation. 13) This might explain the lack of suppression of neutrophil accumulation regardless of the significant inhibition of Th1 cells by anti-αL and -β2.…”

Nutlin-3 inhibits the NFκB Pathway in a p53 Dependent Manner: Implications in Lung Cancer Therapy

“…ICAM-1 mediates cell to cell adhesion and has been shown to play an important role in several diseases including asthma, atherosclerosis, autoimmune disease, ischemia reperfusion injury and acute respiratory distress syndrome. [40][41][42][43][44] ICAM-1 has also been shown to be involved in lung cancer cell invasion, 45 and since elevated levels of ICAM-1 expression has been associated with increased metastasis and poor prognosis in cancer, 46 it is being extensively studied as an important target in cancer therapy. Inhibition of ICAM-1 expression could be a useful tumor response biomarker and also a useful Nutlin-3 Downregulates NFκB Pathway target to decrease metastasis in lung cancer and also potentially other cancers where ICAM-1 levels are elevated.…”

Inflammatory and Bronchospastic Factors in Asthma Exacerbations Caused by Upper Respiratory Tract Infections

“…Furthermore, virus-activated T cells induce shedding of ICAM-1, and circulating sICAM-1 is suggested to be a sensitive marker of T-cell activation in choriomeningitis (Christensen et al 1995). Because intercellular adhesion molecule (ICAM)-1 is the receptor for a major group of RVs (Greve et al 1989), binding of RV to ICAM-1 on T-cells is thought to activate the T-cell function (Stanciu and Djukanovic 1998). Up-regulation of ICAM-1 could increase susceptibility to major group RVs (Greve et al 1989) and lead cells adjacent to infected cells to infection when viruses are released from the cells originally infected.…”