The Role of Selectins During Lung Inflammation and Their Potential Impact for Innovative Therapeutic Strategies

Daniel      Bock; Ewald   M.   Aydt; Wolfgang   M.   Kuebler; Gerhard      Wolff

Abstract

The selectin family of cell adhesion molecules (selectins) is comprised of three structurally related calciumdependent carbohydrate binding proteins, E-, P-, and L-selectin. Located on the surface of endothelial cells (E- and Pselectin), platelets (P-selectin) and of leucocytes (L-selectin), selectins are of vital importance for leukocyte recruitment and accumulation in the vasculature. Based on the unique architecture of the microvasculature of the lung, this task is achieved by two different types of selectin mediated functions (i) tethering and rolling of leukocytes on the pre- and post capillary pulmonary endothelium and in bronchial venules which are mediated by E-, P-, and L-selectin as well as (ii) retention of leukocytes in the pulmonary capillaries by L-selectin. Recent findings in preclinical and clinical research suggest a significant involvement of selectins in both acute and chronic inflammatory lung diseases such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), asthma bronchiale (Asthma), chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). This review summarizes the current progress in understanding the role of selectins during inflammation in the lung and its potential impact for innovative therapeutic strategies.

Keywords: Inflammation, lung diseases, selectins, antagonists and inhibitors

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