Inflammatory cell-endothelium interactions in the allergic inflammatory response

The endothelium participates actively in the development of the inflammatory response, in particular by expressing adhesion molecules and by secreting chimiokines and other cytokines. The severity df allergic asthma is determined in large part by the chronic inflammatory response in the bronchial tree. To elucidate the mechanisms of leukocyte recruitment in allergic asthma, we conducted a study of the endothelium and its interactions with inflammatory cells. In addition to the increase in blood vessel permeability that is a classic feature of the allergic response, we found increased expression of adhesion molecules on bronchial mucosa endothelium from asthma patients. The potential role of alveolar macrophages, T lymphocytes, mastocytes, and eosinophils in activation of the endothelium was investigated. In the course of an allergic response, each of these effector cell types can enhance, via various modalities, adhesion molecule expression and chimiokine secretion by the endothelial cells. The main mediators of these interactions are interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF); IL-4 and histamine are also involved. In status asthmaticus, a condition characterized by extreme inflammation, IL-1 beta and TNF were secreted, suggesting that these cytokines are involved in the development of the inflammation. We have recently cloned and sequenced a molecule called endothelium-specific molecule-1, which may inhibit the adhesion, and therefore the migration, of leukocytes. This discovery and data from studies of endothelium-inflammatory cell interactions have identified new targets for the treatment of asthma.