Integrin expression by eosinophils
Authors: H‐U. Simon
Journal: Allergy (2000)

In many allergic diseases, eosinophils are believed to contribute to the inflammatory process. Adhesion molecules such as integrins play a key role in cell–cell and cell–extracellular matrix interactions. Such interactions are essential for proliferation and differentiation of eosinophils (but also other inflammatory cells) in the bone marrow (1), their migration into the blood (2), their recruitment into tissues (3, 4), and their activation at inflammatory sites (5). Therefore, it is important to study the expression and function of eosinophil adhesion molecules under physiologic and pathologic conditions. Integrins are heterodimeric transmembrane glycoproteins composed of α and β subunits (6). More than 20 heterodimers have been described so far. Integrins have been implicated in the pathogenesis of asthma and other chronic eosinophilic inflammations. For example, β1 integrins (α4β1: very late antigen-4) have been considered to be important for selective recruitment of eosinophils and lymphocytes to inflam-matory sites (3, 4). In contrast, β2 integrins (CD11a-c/CD18) are expressed on all leukocytes, and mediate firm adhesion to vascular endothelium and extracellular matrix proteins (e.g., fibronectin, collagen). In this issue of Allergy, Lundahl et al. observe that β7 integrin surface protein expression is induced during eosinophil differentiation (7). The increase of β7 surface expression was blocked by cycloheximide, suggesting that the newly observed phenomenon was not simply the consequence of redistribution of preformed β7 integrins. In agreement with previous work (8), β7 appeared to associate with α4 to form an α4β7 heterodimer. Since α4 and β1 integrin levels were slightly decreased in these in vitro differentiation assays, it seems that α4 associates less with β1 in mature than immature eosinophils. The functional consequences of less α4β1 and more α4β7 on mature eosinophils are unclear. Both heterodimers serve as ligands for fibronectin, as demonstrated by the study of Lundahl et al. (7). On the other hand, it is likely that α4β1 and α4β7 have different cellular functions. For instance, vascular cell adhesion molecule-1 is a ligand for α4β1, but binds α4β7 only weakly (9, 10). In contrast, mucosal addressin cell adhesion molecule-1 binds α4β7, but not α4β1 (11, 12). This suggests that the differentiation of eosinophils is associated with new properties important for cell–cell and cell–extracellular matrix interactions. Increased β7 integrin expression might be important for at least one step of eosinophil migration from bone marrow to other tissues. However, the importance of eosinophil β7 integrins under physiologic and pathologic conditions in vivo remains to be determined. Besides neutralization or knockout studies to gain insights into the function of a molecule, it is equally important to investigate the structural requirements of that function. Truncation of the cytoplasmic domain of β7 decreases binding to endothelial cells, suggesting that intracellular molecular interactions are important for regulation of integrin avidity. Indeed, there is evidence that activation of cytokine receptors can increase the avidity of integrins, a mechanism that may allow selective activation of these adhesion receptors on certain cells only (13). Further insights into the molecular interactions between eosinophil integrins and their ligands may provide new thera-peutic approaches in chronic allergic disorders. Work in my laboratory is supported by the Swiss National Science Foundation (grant no. 32–58916.99), the EMDO Foundation Zurich, the Saurer Foundation Zurich, and the OPO Foundation Zurich.